Th2 Lymphocytes Research Articles

Comparison of specific in-vitro virulence gene expression and innate host response in locally invasive vs colonizer strains of Streptococcus pneumoniae

Among Rochester NY children, a dramatic increase in nasopharyngeal (NP) colonization by non-vaccine pneumococcal serotypes 35B and 15A occurred during years 2010-2015, after introduction of 13-valent pneumococcal conjugate vaccine (PCV13). In our population, serotype 35B strains colonized in the nasopharynx (NP) but infrequently caused acute otitis media (AOM) whereas serotype 15A strains displayed virulence, evidenced by causing AOM. To explain the virulence difference, virulence genes expression between 35B and 15A, as well as the host's immune response during asymptomatic colonization were analyzed. We investigated differences in regulation of 19 virulence genes for differences in virulence using RT-PCR in 20 35B and 14 15A strains and measured gene expression of 9 host innate cytokines in the NP to assess the mucosal inflammatory response during asymptomatic colonization. Comparing 35B versus 15A strains, genes for competence ComA and RrgC were upregulated; capsular (Cps2D) and virulence genes (PfbA, PcpA and PhtE) were downregulated among 35B strains. PavB, LytA, LytB, NanA, CiaR, PhtD, LuxS, PspA and pneumolysin (Ply) showed no difference. IL17 and IL23 gene expression were > tenfold higher during 35B compared to 15A strain asymptomatic colonization. Only IL23 showed significant difference. In the first 5 years after introduction of PCV13, serotype 35B strains emerged as asymptomatic colonizers and 15A strains emerged to cause AOM in young children. Various genes (PfbA, PcpA, Cps2D and PhtE) among tested in this analysis were downregulated in 35B whereas ComA and RrgC were significantly upregulated. For the host's cytokine response, IL23 proinflammatory response which is essential for the differentiation of Th17 lymphocytes in the NP of children with 35B strains was significantly higher than the response to 15A during asymptomatic colonization.

Inhibition of vascular adhesion protein-1 enhances the anti-tumor effects of immune checkpoint inhibitors.

Modulation of the immunosuppressive tumor microenvironment (TME) is essential for enhancing the anti‐tumor effects of immune checkpoint inhibitors (ICIs). Adhesion molecules and enzymes such as vascular adhesion protein‐1 (VAP‐1), which are expressed in some cancers and tumor vascular endothelial cells, may be involved in the generation of an immunosuppressive TME. In this study, the role of VAP‐1 in TME was investigated in 2 murine colon cancer models and human cancer cells. Intraperitoneal administration of the VAP‐1‐specific inhibitor U‐V296 inhibited murine tumor growth by enhancing IFN‐γ‐producing tumor antigen‐specific CD8+ T cells. U‐V296 exhibited significant synergistic anti‐tumor effects with ICIs. In the TME of mice treated with U‐V296, the expression of genes associated with M2‐like macrophages, Th2 cells (Il4, Retnla, and Irf4), angiogenesis (Pecam1), and fibrosis (Acta2, Loxl2) were significantly decreased, and the Th1/Th2 balance was increased. H2O2, an enzymatic product of VAP‐1, which promoted the production of IL‐4 by mouse Th2 and inhibited IFN‐γ by mouse Th1 and human tumor‐infiltrating lymphocytes, was decreased in tumors and CD31+ tumor vascular endothelial cells in the TMEs of mice treated with VAP‐1 inhibitor. TCGA database analysis showed that VAP‐1 expression was a negative prognostic factor in human cancers, exhibiting a significant positive correlation with IL‐4, IL4R, and IL‐13 expression and a negative correlation with IFN‐γ expression. These results indicated that VAP‐1 is involved in the immunosuppressive TMEs through H2O2‐associated Th2/M2 conditions and may be an attractive target for the development of combination cancer immunotherapy with ICIs.

Liraglutide targets the gut microbiota and the intestinal immune system to regulate insulin secretion.

Liraglutide controls type 2 diabetes (T2D) and inflammation. Gut microbiota regulates the immune system and causes at least in part type 2 diabetes. We here evaluated whether liraglutide regulates T2D through both gut microbiota and immunity in dysmetabolic mice. Diet-induced dysmetabolic mice were treated for 14days with intraperitoneal injection of liraglutide (100µg/kg) or with vehicle or Exendin 4 (10µg/kg) as controls. Various metabolic parameters, the intestinal immune cells were characterized and the 16SrDNA gene sequenced from the gut. The causal role of gut microbiota was shown using large spectrum antibiotics and by colonization of germ-free mice with the gut microbiota from treated mice. Besides, the expected metabolic impacts liraglutide treatment induced a specific gut microbiota specific signature when compared to vehicle or Ex4-treated mice. However, liraglutide only increased glucose-induced insulin secretion, reduced the frequency of Th1 lymphocytes, and increased that of TReg in the intestine. These effects were abolished by a concomitant antibiotic treatment. Colonization of germ-free mice with gut microbiota from liraglutide-treated diabetic mice improved glucose-induced insulin secretion and regulated the intestinal immune system differently from what observed in germ-free mice colonized with microbiota from non-treated diabetic mice. Altogether, our result demonstrated first the influence of liraglutide on gut microbiota and the intestinal immune system which could at least in part control glucose-induced insulin secretion.

Chemokine Profiles Are Affected in Serum of Patients with Acute Rejection of Kidney Allograft.

Kidney allograft transplantation improved the prognosis and quality of life of patients with end-stage renal diseases but the occurrence of acute rejection represents a limitation of the final outcome. Noninvasive biomarkers are needed as well as further advancements in the understanding of immune mechanisms of reaction to the allograft. Our study of 138 patients focused on one-year monitoring of serum concentrations of 12 chemokines regulating the recruitment of different immune cells into transplanted allograft and on in vitro regulation of the same chemokines release by interactions of renal proximal epithelial cells with monocyte/macrophage cell line stimulated with TNF alpha. In a group of 44 patients with acute rejection, higher serum pretransplant levels of CXCL1, CXCL5, CXCL6, CCL2, CCL21, and particularly CXCL10 and CX3CL1(both p < 0.001) were found suggesting their higher proinflammatory status as compared to subjects with the uncomplicated outcome. In samples collected at the day of biopsy positive for acute rejection, chemokines CXCL9 and CXCL11 attracting preferentially Th1 lymphocytes were found to be upregulated. In our in vitro model with TNF alpha induction, renal proximal epithelial cells seemed to be a more potent source of chemokines attracting neutrophils as compared to monocyte/macrophage cell line but the coculture of these cells potentiated release of neutrophilic chemokines CXCL5 and CXCL6. Similar augmentation of chemokine production was found also in the case of CCL2. On the other hand, adding of monocytes/macrophages to a culture of renal epithelial cells suppressed the release of CXCL10 and CXCL11 attracting T lymphocytes. We assume from our data that in kidney allograft transplantation, chemokines attracting neutrophils, T lymphocytes, and monocytes are induced simultaneously and measurement some of them in combination might be used as biomarkers of acute rejection. Mutual cell-cell interactions of immune cells with renal parenchyma seem to be important for fine regulation of chemokine release.

Effects of Hyperbaric Oxygen Therapy in Children with Severe Atopic Dermatitis.

In the course of atopic dermatitis (AD), the overactivity of the immune system, associated with predominant Th2 lymphocyte responses, is observed, which leads to an increased inflammatory reaction. Cases of a severe course of atopic dermatitis lead to the search for new therapeutic options. The aim of this study was to assess the effects of hyperbaric oxygen therapy (HBOT) treatment for severe cases of AD in children. A total of 15 children with severe AD underwent therapy. The influence of HBOT on the clinical course of AD and immunomodulatory effect of the therapy was analyzed by the SCORAD and objective SCORAD (oSCORAD) scales and by determining the serum concentration of immunological parameters (blood: nTreg lymphocytes, CD4+CD25highCD127-FOXP3+, NKT lymphocytes CD3+, CD16/56+, and serum: total IgE, cytokines IL-4, IL-6, and IL-10, before and after the 30-day treatment cycle). The study showed a significant effect of the therapy on the improvement of the skin condition. In all children, a reduction in the extent and intensity of skin lesions, reduction of redness, swelling, oozing/crusting, scratch marks and skin lichenification after HBOT was observed. Patients also reported a reduction in the intensity of pruritus and an improvement in sleep quality after therapy. In all children, a statistically significant decrease in the serum level of IgE was observed. However, no statistically significant changes in the blood levels of IL-4, IL-6 and IL-10, as well as the percentage of CD4+CD25highCD127−FOXP3+ Treg and NKT lymphocytes, were found. In conclusion, the use of hyperbaric therapy has a positive impact on treatment results in children with a severe course of atopic dermatitis.

Genome-wide association study of resistance to Mycobacterium tuberculosis infection identifies a locus at 10q26.2 in three distinct populations.

The natural history of tuberculosis (TB) is characterized by a large inter-individual outcome variability after exposure to Mycobacterium tuberculosis. Specifically, some highly exposed individuals remain resistant to M. tuberculosis infection, as inferred by tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). We performed a genome-wide association study of resistance to M. tuberculosis infection in an endemic region of Southern Vietnam. We enrolled household contacts (HHC) of pulmonary TB cases and compared subjects who were negative for both TST and IGRA (n = 185) with infected individuals (n = 353) who were either positive for both TST and IGRA or had a diagnosis of TB. We found a genome-wide significant locus on chromosome 10q26.2 with a cluster of variants associated with strong protection against M. tuberculosis infection (OR = 0.42, 95%CI 0.35-0.49, P = 3.71×10-8, for the genotyped variant rs17155120). The locus was replicated in a French multi-ethnic HHC cohort and a familial admixed cohort from a hyper-endemic area of South Africa, with an overall OR for rs17155120 estimated at 0.50 (95%CI 0.45-0.55, P = 1.26×10-9). The variants are located in intronic regions and upstream of C10orf90, a tumor suppressor gene which encodes an ubiquitin ligase activating the transcription factor p53. In silico analysis showed that the protective alleles were associated with a decreased expression in monocytes of the nearby gene ADAM12 which could lead to an enhanced response of Th17 lymphocytes. Our results reveal a novel locus controlling resistance to M. tuberculosis infection across different populations.

Cav1 channels is also a story of non excitable cells: Application to calcium signalling in two different non related models

Calcium is a second messenger essential, in all cells, for most cell functions. The spatio-temporal control of changes in intracellular calcium concentration is partly due to the activation of calcium channels. Voltage-operated calcium channels are present in excitable and non-excitable cells. If the mechanism of voltage-operated calcium channels is well known in excitable cells the Ca2+ toolkit used in non-excitable cells to activate the calcium channels is less described. Herein we discuss about very similar pathways involving voltage activated Cav1 channels in two unrelated non-excitable cells; ectoderm cells undergoing neural development and effector Th2 lymphocytes responsible for parasite elimination and also allergic diseases. We will examine the way by which these channels operate and are regulated, as well as the consequences in terms of gene transcription. Finally, we will consider the questions that remain unsolved and how they might be a challenge for the future.

Role of polyphenols in the prevention of immunoinflammatory diseases

Inflammation has been described as an initiator event of major diseases with significant impact in terms of public health such as cardiovascular diseases, autoimmune diseases, eye diseases, age-related diseases and more particularly neurodegenerative diseases, or the occurrence and development of cancers. Among the microcomponents of the diet which can participate in a prevention of inflammation and subsequently to various associated diseases, polyphenols from different origins such as resveratrol, could be good candidates. Indeed, in this presentation, we highlight the potential effect of polyphenol on both interleukins secretion by pro-inflammatory lymphocytes Th17 and on the lymphocyte differentiation. In this process, we demonstrate the main role of the NAD-dependent deacetylase, Sirtuin 1 and of the nuclear factor STAT3. T lymphocytes that are not only the cells where the STAT3 factor plays an important role, it is also the case of macrophages where this nuclear factor makes it possible to activate the transcription of genes encoding pro-inflammatory interleukins such as interleukin-6 and -8. Furthermore, macrophages are also able to produce interleukin-1β from an inflammatory complex namely inflammasome. In this way, polyphenols could reduce interleukin-6 level thus down regulates STAT3 activation in macrophages, leading to the impairment of the running inflammatory amplification loop between macrophages and chondrocytes and subsequently could reduce some inflammatory diseases such as arthritis.

Levels of low-molecular-weight hyaluronan in periodontitis-treated patients and its immunostimulatory effects on CD4+ T lymphocytes.

During periodontitis, chronic inflammation triggers soft tissue breakdown, and hyaluronan is degraded into fragments of low molecular weight (LMW-HA). This investigation aimed to elucidate whether LMW-HA fragments with immunogenic potential on T lymphocytes remain in periodontal tissues after periodontal treatment. GCF samples were obtained from 15 periodontitis-affected patients and the LMW-HA, RANKL, and OPG levels were analyzed before and after 6 months of periodontal treatment by ELISA. Eight healthy individuals were analyzed as controls. Besides, human T lymphocytes were purified, exposed to infected dendritic cells, and pulsed with LMW-HA. Non-treated T lymphocytes were used as control. The expression levels of the transcription factors and cytokines that determine the Th1, Th17, and Th22 lymphocyte differentiation and function were analyzed by RT-qPCR. Similarly, the expression levels of RANKL and CD44 were analyzed. In the GCF samples of periodontitis-affected patients, higher levels of LMW-HA were detected when compared with those of healthy individuals (52.1 ± 15.4 vs. 21.4 ± 12.2, p < 0.001), and these increased levels did not decrease after periodontal therapy (52.1 ± 15.4 vs. 45.7 ± 15.9, p = 0.158). Similarly, the RANKL levels and RANKL/OPG ratios did not change after periodontal therapy. Furthermore, in human T lymphocytes, LMW-HA induced higher expression levels of the Th1, Th17, and Th22-related transcription factors and cytokines, as well as CD44 and RANKL, as compared with non-treated cells. In some patients, increased levels of LMW-HA persist in periodontal tissues after conventional periodontal therapy, and these remaining LMW-HA fragments with immunostimulatory potential could induce the polarization of a pathologic Th1/Th17/Th22-pattern of immune response on T lymphocytes. The persistence of increased levels of LMW-HA in periodontal tissues after periodontal therapy could favor the recurrence of the disease and further breakdown of periodontal supporting tissues.

Artocarpus tonkinensis Extract Inhibits LPS-Triggered Inflammation Markers and Suppresses RANKL-Induced Osteoclastogenesis in RAW264.7

Artocarpus tonkinensis (At) leaf decoction, a traditional remedy prepared in North Vietnam by the Hmong ethnic group, is a tea extract rich in bioactive compounds that may have therapeutic effects in arthritis and backache. Indeed, it has been demonstrated that At is able to inhibit Th17 lymphocytes development and to protect mice in an experimental model of collagen-induced arthritis. By resorting to macrophage in vitro models of inflammation and osteoclastogenesis, we showed that At extract significantly reduced nitric oxide synthase 2 (NOS2) activity and IL-6 production by RAW 264.7 murine cells. Moreover, At demonstrated an anti-osteoclastogenic effect, as revealed by complete inhibition of TRAP-positive osteoclast formation and decreased expression of key osteoclast-related genes. This At activity likely relies on the inhibition of RANK downstream signaling pathway, as the activation of non-receptor tyrosine kinase Src is reduced upon RANKL-At exposure. Protective effect of At against bone loss was also enlightened in vivo by collagen-induced arthritis (CIA) experiment demonstrating that, although paw edema was only weakly opposed by drinking At decoction, bone and cartilage were well preserved in CIA+At mice and joint tissue expressed decreased levels of osteoclast marker genes respect to CIA control group. Maesopsin 4-O-β-D-glucoside (i.e., TAT-2, one of the main decoction bioactive components) was capable to contrast NOS2 activity, IL-6 expression and osteoclast formation, too, albeit to a lesser extent when compared to At decoction. Overall, this study enlightens another At cell target, macrophages, beside Th17 lymphocytes, and suggests that the anti-arthritic beneficial effects of At decoction largely derives from its ability to counteract not only inflammation, but also osteoclastogenesis.

Multi-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients

Patients with liver cirrhosis may develop minimal hepatic encephalopathy (MHE) which affects their quality of life and life span. It has been proposed that a shift in peripheral inflammation triggers the appearance of MHE. However, the mechanisms involved in this immune system shift remain unknown. In this work we studied the broad molecular changes involved in the induction of MHE with the goal of identifying (1) altered genes and pathways in peripheral blood cells associated to the appearance of MHE, (2) serum metabolites and cytokines with modified levels in MHE patients and (3) MHE-regulated immune response processes related to changes in specific serum molecules. We adopted a multi-omic approach to profile the transcriptome, metabolome and a panel of cytokines of blood samples taken from cirrhotic patients with or without MHE. Transcriptomic analysis supports the hypothesis of alternations in the Th1/Th2 and Th17 lymphocytes cell populations as major drivers of MHE. Cluster analysis of serum molecules resulted in six groups of chemically similar compounds, suggesting that functional modules operate during the induction of MHE. Finally, the multi-omic integrative analysis suggested a relationship between cytokines CCL20, CX3CL1, CXCL13, IL-15, IL-22 and IL-6 with alteration in chemotaxis, as well as a link between long-chain unsaturated phospholipids and the increased fatty acid transport and prostaglandin production. We found altered immune pathways that may collectively contribute to the mild cognitive impairment phenotype in MHE. Our approach is able to combine extracellular and intracellular information, opening new insights to the understanding of the disease.

Nucleocapsid and Spike Proteins of the Coronavirus SARS-CoV-2 Induce IL6 in Monocytes and Macrophages-Potential Implications for Cytokine Storm Syndrome.

The pandemic of the new coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has led to the deaths of more than 1.5 million people worldwide. SARS-CoV-2 causes COVID-19, which exhibits wide variation in the course of disease in different people, ranging from asymptomatic and mild courses to very severe courses that can result in respiratory failure and death. Despite the rapid progression of knowledge, we still do not know how individual cells of the immune system interact with the virus or its components, or how immune homeostasis becomes disrupted, leading to the rapid deterioration of a patient’s condition. In the present work, we show that SARS-CoV-2 proteins induce the expression and secretion of IL-6 by human monocytes and macrophages, the first line cells of antiviral immune responses. IL-6 may play a negative role in the course of COVID-19 by inhibiting Th1-dependent immunity and stimulating Th17 lymphocytes, thus leading to an increased probability of a cytokine storm.

Catgut Implantation at Acupoints has an Immunosuppressive Effect on Autoimmune Uveitis by Regulating Th1/Th17 Lymphocytes

Catgut implantation at acupoints (CIA) has a long history as a medical treatment for a wide variety of diseases, including autoimmune diseases. However, the effect and mechanism of this therapy in autoimmune uveitis is still largely unknown. The aim of this study was to explore the immunity-inhibitory effect of CIA in an experimental autoimmune uveitis (EAU) rat model. EAU was established in Lewis rats by the injection of IRBP1177–1191 peptide. The rats were randomly divided into control and CIA groups. Phenotypic and histological assessments were performed days 9, 13, 18, 23 post-immunization. The percentage of Th1 and Th17 lymphocytes isolated from lymph nodes were determined by flow cytometry. The expression of IL-17 and IFN-γ was detected by real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA). In the CIA group, delayed mild inflammation was observed. Pathological investigation found alleviated infiltration of lymphocytes and ocular damage. Flow cytometry showed significantly decreased Th17 lymphocytes at day 9, 13, and 18 post-immunization (P&lt;0.05) and no significant changes at day 23 post-immunization (P=0.868) after CIA. The Th1 lymphocytes were significantly decreased at day 13 and 18 post-immunization (P&lt;0.05) and comparable at day 9 (P=0.111) and 23 (P=0.551) post-immunization in the CIA group. IL-17 and IFN-γ mRNA levels were notably decreased at day 9, 13 and 18 post-immunization (P&lt;0.05) and showed a downward trend at day 23 post-immunization, although with no significance (P=0.080 and P=0.137, respectively) after CIA. Serum IL-17 and IFN-γ levels in the CIA group were significantly decreased at day 9, 13 and 18 post-immunization (P&lt;0.05) and were comparable at day 23 post-immunization (P=0.078 and P=0.979, respectively). Ocular inflammation was markedly inhibited after catgut implantation at Pishu (BL20) and Shenshu (BL23) acupoints in an EAU rat model. Moreover, CIA reduced Th1 and Th17 lymphocytes and the expression IFN-γ and IL-17.

High-altitude hypoxia exacerbates dextran sulfate sodium (DSS)-induced colitis by upregulating Th1 and Th17 lymphocytes

ABSTRACT High altitude hypoxia (HAH) involves the pathogenesis of ulcerative colitis (UC) and gastrointestinal erosions. However, the mechanism of effects of HAH in colitis remains controversial. This study reports the immunomodulation mediated by HAH to enhancing the severity of UC in the mice model. BALB/c mice were used to establish the UC model by dextran sulfate sodium (DSS) compared to wild type mice. Mice groups were exposed to hypoxic conditions in a hypobaric chamber with an altitude of 5000 m for 7 days. Then, Spleen, mesenteric lymph nodes and colon tissues were collected. The activity of UC, the infiltration of the immune cells, and the released cytokines were investigated. Results showed that the severity of DSS-induced UC significantly increased in mice exposed to HAH. The analysis of pathological changes showed increased weight loss and decreased colon length accompanied by diarrhea and bloody feces in the hypobaric hypoxia group. Interestingly, the levels of inflammatory cytokines IL-17, TNF-α, and IFN-γ in the spleen and mesenteric lymph node showed a significant increase within the colon of the hypobaric hypoxia group. The population of Th 1 and Th 17 cells in the spleen was significantly increased in mice exposed to hypobaric hypoxia compared NC group. Suggesting that high altitude hypoxia enhances colitis in mice through activating the increase of inflammatory Th1 and Th17 lymphocytes. In conclusion, this study revealed that hypobaric hypoxia directly increases the severity of UC in the mice model via increasing the activity of inflammatory CD4+ Th1 and Th 17 lymphocytes.

Predicted regulatory SNPs reveal potential drug targets and novel companion diagnostics in psoriasis

Psoriasis is an autoimmune disease associated with interleukins, their receptors, key transcription factors and more recently, antimicrobial peptides (AMPs). Cathelicidin LL-37 is an AMP proposed to play a fundamental role in psoriasis etiology. With our proprietary software SNPClinic v.1.0, we analyzed 203 common SNPs (MAF frequency ​> ​1%) in proximal promoters of 22 genes associated with psoriasis. These include nine genes which protein products are classic drug targets for psoriasis (TNF, IL17A, IL17B, IL17C, IL17F, IL17RA, IL12A, IL12B and IL23A). SNPClinic predictions were run with DNAseI-HUP chromatin accessibility data in eight psoriasis/epithelia-relevant cell lines from ENCODE including keratinocytes (NHEK), TH1 and TH17 lymphocytes. Results were ranked quantitatively by transcriptional relevance according to our novel Functional Impact Factor (FIF) parameter. We found six rSNPs in five genes (CAMP/cathelicidin, S100A7/psoriasin, IL17C, IL17RA and TNF) and each was confirmed as true rSNP in at least one public eQTL database including GTEx portal and ENCODE (Phase 3). Predicted regulatory SNPs in cathelicidin, IL17C and IL17RA genes may explain hyperproliferation of keratinocytes. Predicted rSNPs in psoriasin, IL17C and cathelicidin may contribute to activation and polarization of lymphocytes. Predicted rSNPs in TNF gene are concordant with the epithelium-mesenchymal transition. In spite that these results must be validated in vitro and in vivo with a functional genomics approach, we propose FOXP2, RUNX2, NR2F1, ELF1 and HESX1 transcription factors (those with the highest FIF on each gene) as novel drug targets for psoriasis. Furthermore, four out of six rSNPs uncovered by SNPClinic v.1.0 software, could also be validated in the clinic as companion diagnostics/pharmacogenetics assays for psoriasis prescribed drugs that block TNF-α (e.g. Etanercept), IL-17 (e.g. Secukinumab) and IL-17 receptor (Brodalumab).

Comparison of serum concentrations of interleukins 10, 12, 17 and 35 between patients with alopecia areata and controls.

IntroductionAlopecia areata (AA) is one of the most common causes of non-scarring hair loss in adults and children with unknown etiopathogenesis, however immunological factors play an important role.AimTo evaluate the concentration of interleukin (IL) 10 (IL-10), IL-12, IL-17 and IL-35 in the blood serum of patients with AA.Material and methodsAA study group consisted of 118 patients. The control group consisted of 54 healthy individuals. The severity of the disease was assessed by SALT score. In the study group, the percentage of hair loss averaged 49.6% ±36.3%. The concentration of IL-10, IL-12, IL-17 and IL-35 in the serum was assessed by the enzyme-linked immunosorbent assays (ELISA).ResultsIn patients with AA, the level of IL-12 and IL-17 was significantly higher than in the control group (p > 0.05). The level of IL-10 in patients was slightly higher, whereas the level of IL-35 was slightly lower, compared to the control group, but those differences were not statistically significant. Furthermore, in patients with more severe disease the IL-12 level was significantly higher as compared to patients with the less severe AA (p < 0.05).ConclusionsThe etiopathogenesis of AA is complex, however Th1 and Th17 lymphocytes and their increased activity are undoubtedly significant contributors in this process. Disorders of immunological processes in AA require further research in order to understand the underlying pathomechanisms of the disease and to provide potential therapeutic strategies.

The Morphofunctional Response of T-lymphocytes to in vitro Contact with a Calcium Phosphate Coating in the Presence of a T-cell Activator

The paper reports a study of the morphofunctional activity of T-lymphocytes in response to the in vitro contact with calcium phosphate (CP) coating in the presence of the particles bearing antibodies against CD2, CD3, and CD28 antigens. VT1-0 titanium plates (10 × 10 × 1 mm3) with a double-sided microarc rough (Ra = 2–5 µm) CP coating were used as the model samples of the mineral matrix of the bone tissue. Magnetic particles (MACSiBeadTM T-cell Activation/Expansion Kit human) bearing antibodies to CD2, CD3, and CD28 antigens were used as a T-cell activator (TCA) simulating the signals produced by antigen-presenting cells (APCs). Mononuclear cells (MNCs) isolated from human blood (98.8% of CD45CD3+ cells) were cultured in the presence of samples with a CP coating and/or TCA (2 × 106 particles in 1.5 mL of nutritive medium in the proportion of 2 : 1 to cells) for 2 and 14 days. The CP coating and TCA triggered MNC culture adaptation in a synergic way via the mechanisms of hyperactivation and subsequent death of T-lymphocytes. Immune selection occurred through the accumulation of the naive CD45RA+/RO+ T-lymphocytes and memory T-cells with the simultaneous depletion of the CD4+ and CD8+ T-cell pool. The shift in the T-lymphocyte populations was observed together with the increase (after 48 h of culturing) in the cell secretion activity with its subsequent decrease by the 14th day of observation. CP coating sustained (compared with the cell culture grown on plastic) the secretion ability of Th1 (IL-12, TNFα, and IFNγ) and Th2 (IL-4, IL-6, IL-10, and IL-13) lymphocytes. At the same time, the prolonged TCA signal after the 48-h activation caused the depletion of T-cell secretion. The suggestion that the observed in vitro effects may play role in the switching of signaling between T-lymphocytes, APCs, and CP materials at the cell–foreign body interface, which may result in a change in the inflammation phase, development of immune tolerance, successful osseointegration of the implant, or bone tissue remodeling impairment, is discussed.

The immunomodulating role of probiotics in the prevention and treatment of oral diseases.

Probiotics are defined as non-pathogenic live microorganisms which, when administered in appropriate amounts, are beneficial to the health of the host. Currently, the group of probiotic microorganisms includes bacteria that produce lactic acid of the genera Lactobacillus and Bifidobacterium, belonging to the so-called LAB (lactic acid bacteria) groups, and the yeast Saccharomyces boulardii. Probiotics have a protective role in Candida spp. oral infection and especially colonization. Lactobacillus limits the progression of chronic periodontitis by inhibiting the secretory activity of Th17 lymphocytes, which in the pathogenesis of this disease are responsible for an excessive cytokine response causing adverse changes in periodontal tissues. A meta-analysis of the results of studies on the clinical evaluation of the effectiveness of probiotics in the treatment of gingivitis showed that the use of probiotics improved the condition of the gums in the course of the therapeutic process. Regular use of probiotics during orthodontic treatment significantly reduces the number of bacteria from the Streptococcus mutans group in the patient’s saliva and significantly inhibits the expression of inflammatory mediators and an excessive immune response. The main mechanisms of the action of probiotics, such as elimination and inhibition of the growth of pathogenic microorganisms through competition for receptor sites and the secretion of metabolites with antibacterial activity, as well as the stimulation of specific and non-specific immune responses by activating T lymphocytes, and stimulating the production of cytokines, make it possible to also effectively use pro-health bacteria in oral diseases.

MicroRNAs as the Important Regulators of T Helper 17 Cells: A Narrative Review.

T helper (Th)-17 cells are a distinct and important subset of Th cells and their functions are due to the ability of production and secretion of key cytokines in the immune system such as interleukin (IL)-17, IL-22, IL-21, and tumor necrosis factor-α (TNF-α). According to these cytokines, these cells have vital roles in the pathogenesis of the disease such as rheumatoid arthritis (RA) and osteoarthritis (OA). Nowadays, microRNAs (miRNAs) are defined as essential regulators of cell function by targeting transcription factors and other elements that act in cells to control gene expression. The purpose of this study was to detect and investigate articles evaluating the function of miRNA in Th-17 cell performance. The language was restricted to English and the search was done in PubMed, Web of Science and Embase. In this review, we first explain the role of effective factors in the function of Th17 lymphocytes, and then, we summarize the performance of several miRNAs involved in the activation and appropriate functions of Th17 cells in the immune system.

Relación entre carga parasitaria y linfocitos Th1 en biopsias de piel de perros con leishmaniosis

&lt;div&gt;La leishmaniosis visceral (LV) es una enfermedad sistémica crónica severa causada por Leishmania donovani o L. infantum. Varios estudios han demostrado que la susceptibilidad a LV está relacionada a altos títulos de anticuerpos circulantes y a una depresión de la inmunidad mediada por linfocitos Th1, principalmente con disminución de la producción de interferon (IFN-γ) e interleukina (IL-12). Similar a la humana, la LV canina está caracterizada por activación policlonal de células B e inmunosupresión específica. El objetivo del trabajo fue establecer la relación entre la carga parasitaria y la respuesta inmune en perros con LV. Se seleccionaron pacientes caninos con diagnóstico serológico reactivo a LV y se les extrajeron muestras para examen parasitológico directo y biopsias de piel del pabellón auricular para efectuar la técnica inmunohistoquímica con el fin de detectar linfocitos Th1 en relación con la carga parasitaria. En muestras de animales sin síntomas que registraban una elevada carga parasitaria, la cantidad de Th1 no superaba las 4 células por campo de mayor aumento, mientras que, en las muestras donde prevalecían cargas moderadas y bajas de parásitos, la cantidad de Th1 superaban las 8 células por campo de mayor aumento, pudiendo llegar hasta 10. De las muestras provenientes de animales con síntomas se observó que en aquéllas con moderada o elevada carga de parásitos, la cantidad de linfocitos Th1 no superaba las 5 células, mientras que las muestras con baja carga parasitaria superaban las 8 células por campo de mayor aumento. Se concluye que la presencia o ausencia de sintomatología en caninos con LV no depende de la carga parasitaria encontrada en las biopsias de piel. Por otra parte, se observó que la alta carga parasitaria se relaciona con inmunosupresión mediada por linfocitos Th1, mientras que en los animales con alta respuesta inmunológica, la carga parasitaria fue baja.&lt;/div&gt;La leishmaniosis visceral (LV) es una enfermedad sistémica crónicasevera causada por Leishmania donovani o L. infantum. Varios estudios han demostradoque la susceptibilidad a LV está relacionada a altos títulos de anticuerpos circulantes y a unadepresión de la inmunidad mediada por linfocitos Th1, principalmente con disminución dela producción de interferon (IFN-γ) e interleukina (IL-12). Similar a la humana, la LV caninaestá caracterizada por activación policlonal de células B e inmunosupresión específica. Elobjetivo del trabajo fue establecer la relación entre la carga parasitaria y la respuesta inmuneen perros con LV. Se seleccionaron pacientes caninos con diagnóstico serológico reactivo aLV y se les extrajeron muestras para examen parasitológico directo y biopsias de piel del pabellónauricular para efectuar la técnica inmunohistoquímica con el fin de detectar linfocitosTh1 en relación con la carga parasitaria. En muestras de animales sin síntomas que registrabanuna elevada carga parasitaria, la cantidad de Th1 no superaba las 4 células por campode mayor aumento, mientras que, en las muestras donde prevalecían cargas moderadas ybajas de parásitos, la cantidad de Th1 superaban las 8 células por campo de mayor aumento,pudiendo llegar hasta 10. De las muestras provenientes de animales con síntomas se observóque en aquéllas con moderada o elevada carga de parásitos, la cantidad de linfocitos Th1 nosuperaba las 5 células, mientras que las muestras con baja carga parasitaria superaban las 8células por campo de mayor aumento. Se concluye que la presencia o ausencia de sintomatologíaen caninos con LV no depende de la carga parasitaria encontrada en las biopsias depiel. Por otra parte, se observó que la alta carga parasitaria se relaciona con inmunosupresiónmediada por linfocitos Th1, mientras que en los animales con alta respuesta inmunológica,la carga parasitaria fue baja.