Activation Of Th1 Cells Research Articles

The Host Peritoneal Cavity Harbors Prominent Memory Th2 and Early Recall Responses to an Intestinal Nematode.

Intestinal parasitic nematodes affect a quarter of the world’s population, typically eliciting prominent effector Th2-driven host immune responses. As not all infected hosts develop protection against reinfection, our current understanding of nematode-induced memory Th2 responses remains limited. Here, we investigated the activation of memory Th2 cells and the mechanisms driving early recall responses to the enteric nematode Heligmosomoides polygyrus in mice. We show that nematode-cured mice harbor memory Th2 cells in lymphoid and non-lymphoid organs with distinct transcriptional profiles, expressing recirculation markers like CCR7 and CD62-L in the mesenteric lymph nodes (mLN), and costimulatory markers like Ox40, as well as tissue homing and activation markers like CCR2, CD69 and CD40L in the gut and peritoneal cavity (PEC). While memory Th2 cells persist systemically in both lymphoid and non-lymphoid tissues following cure of infection, peritoneal memory Th2 cells in particular displayed an initial prominent expansion and strong parasite-specific Th2 responses during early recall responses to a challenge nematode infection. This effect was paralleled by a significant influx of dendritic cells (DC) and eosinophils, both also appearing exclusively in the peritoneal cavity of reinfected mice. In addition, we show that within the peritoneal membrane lined by peritoneal mesothelial cells (PeM), the gene expression levels of cell adhesion markers VCAM-1 and ICAM-1 decrease significantly in response to a secondary infection. Overall, our findings indicate that the host peritoneal cavity in particular harbors prominent memory Th2 cells and appears to respond directly to H. polygyrus by an early recall response via differential regulation of cell adhesion markers, marking the peritoneal cavity an important site for host immune responses to an enteric pathogen.

Low Activation of CD8+ T Cells in response to Viral Peptides in Mexican Patients with Severe Dengue.

It is acknowledged that antiviral immune response contributes to dengue immunopathogenesis. To identify immunological markers that distinguish dengue fever (DF) and dengue hemorrhagic fever (DHF), 113 patients with confirmed dengue infection were analyzed at 6 or 7 days after fever onset. Peripheral blood mononuclear cells (PBMC) were isolated, lymphocyte subsets and activation biomarkers were identified by flow cytometry, and differentiation of T helper (Th) lymphocytes was achieved by the relative expression analysis of T-bet (Th1), GATA-3 (Th2), ROR-γ (Th17), and FOXP-3 (T regulatory) transcription factors quantified by real-time PCR. CD8+, CD40L+, and CD45+ cells show higher numbers in DF compared to DHF patients, whereas CD4+, CD19+, and CD25+ cells show higher numbers in DHF than DF patients. High expression of GATA-3 accompanied by low expression of T-bet indicates predominance of Th2 response. In addition, higher expression of FOXP-3 and reduced functional cytotoxic T cells (CD8+perforin+) were observed in DHF patients. In further experiments, PBMC were stimulated ex vivo with dengue virus E, NS3, NS4, and NS5 peptides, and proliferating T cell subsets were determined. Lower proliferative responses to NS3 and NS4 peptides and reduced CD8+ cytotoxic T cells were observed in DHF patients. Our results suggest that immune response to dengue is dysregulated with predominance of CD4+ T cells, low activation of Th1 cells, and downregulation of the antiviral cytotoxic activity during severe dengue, likely induced by regulatory T cells.

Role of interleukin-4 and their antagonistic effect in asthma

Asthma is a chronic inflammatory disease of the lower airways, characterize by wheezing cough, chest tightness along with inflammation of airway and shortness of breath. Allergens like environmental substance are predispose asthmatics patients to allergy. Mast cells produced interleukin (IL)- 4 which either activate signal transducer and activator of transcription 6 (STAT-6) pathway that involved in differentiation of na ve T-cells to TH2 or activation of TH2 cells indirectly. The aim of the current context is to present role of IL-4 in asthma and effect as antagonist. IL-4 results in increased mucus production and involve in IgE synthesis from B cells. IL4 facilitate chemotaxis and aid in displaying of VCAM-1 which attract eosinophil basophils monocytes T-lymphocytes to blood vessel. IL4 inhibit apoptosis either by preventing decrease in BCL-2 level or binding of FasL to Fas (cd32) receptor which result in acute allergic response. Elevated level of IL-4 has greatly adverse impact on asthmatic patients so by decreasing the level of IL-4 will greatly reduce asthma phenotype.

Therapeutic targeting miR130b counteracts diffuse large B-cell lymphoma progression via OX40/OX40L-mediated interaction with Th17 cells

MicroRNAs (miRNAs) are involved in lymphoma progression by regulating the tumor microenvironment. Serum miR130b is overexpressed in diffuse large B-cell lymphoma (DLBCL), inducing Th17 cell alterations. To further illustrate its biological significance and therapeutic rationale, miR130b was detected by quantitative real-time PCR in the serum samples of 532 newly diagnosed DLBCL patients. The mechanism of miR130b on lymphoma progression and the tumor microenvironment was investigated both in vitro and in vivo. Therapeutic targeting miR130b was also evaluated, including OX40 agonistic antibody and lipid nanoparticles (LNPs)-miR130b antagomir. The results showed that serum miR130b significantly correlated with tumor miR130b and serum interleukin-17, indicating lymphoma relapse and inferior survival of DLBCL patients. MiR130b overexpression altered tumor microenvironment signaling pathways and increased Th17 cell activity. As mechanism of action, miR130b downregulated tumor OX40L expression by directly targeting IFNAR1/p-STAT1 axis, recruiting Th17 cells via OX40/OX40L interaction, thereby promoting immunosuppressive function of Th17 cells. In co-culture systems of B-lymphoma cells with immune cells, miR130b inhibited lymphoma cell autophagy, which could be counteracted by OX40 agonistic antibody and LNPs-miR130b antagomir. In murine xenograft model established with subcutaneous injection of A20 cells, both OX40 agonistic antibody and LNPs-miR130b antagomir remarkably inhibited Th17 cells and retarded miR130b-overexpressing tumor growth. In conclusion, as an oncogenic biomarker of DLBCL, miR130b was related to lymphoma progression through modulating OX40/OX40L-mediated lymphoma cell interaction with Th17 cells, attributing to B-cell lymphoma sensitivity towards OX40 agonistic antibody. Targeting miR130b using LNPs-miR130b antagomir could also be a potential immunotherapeutic strategy in treating OX40-altered lymphoid malignancies.

Programming of Vascular Dysfunction by Maternal Stress: Immune System Implications.

A growing body of evidence highlights that several insults during pregnancy impact the vascular function and immune response of the male and female offspring. Overactivation of the immune system negatively influences cardiovascular function and contributes to cardiovascular disease. In this review, we propose that modulation of the immune system is a potential link between prenatal stress and offspring vascular dysfunction. Glucocorticoids are key mediators of stress and modulate the inflammatory response. The potential mechanisms whereby prenatal stress negatively impacts vascular function in the offspring, including poor hypothalamic–pituitary–adrenal axis regulation of inflammatory response, activation of Th17 cells, renin–angiotensin–aldosterone system hyperactivation, reactive oxygen species imbalance, generation of neoantigens and TLR4 activation, are discussed. Alterations in the immune system by maternal stress during pregnancy have broad relevance for vascular dysfunction and immune-mediated diseases, such as cardiovascular disease.

The Purinergic Receptor P2X4 Promotes Th17 Activation and the Development of Arthritis.

Purinergic signaling plays a major role in T cell activation leading to IL-2 production and proliferation. However, it is unclear whether purinergic signaling contributes to the differentiation and activation of effector T cells. In this study, we found that the purinergic receptor P2X4 was associated with human Th17 cells but not with Th1 cells. Inhibition of P2X4 receptor with the specific antagonist 5-BDBD and small interfering RNA inhibited the development of Th17 cells and the production of IL-17 by effector Th17 cells stimulated via the CD3/CD28 pathway. Our results showed that P2X4 was required for the expression of retinoic acid-related orphan receptor C, which is the master regulator of Th17 cells. In contrast, inhibition of P2X4 receptor had no effect on Th1 cells and on the production of IFN-γ and it did not affect the expression of the transcription factor T-bet (T-box transcription factor). Furthermore, inhibition of P2X4 receptor reduced the production of IL-17 but not of IFN-γ by effector/memory CD4+ T cells isolated from patients with rheumatoid arthritis. In contrast to P2X4, inhibition of P2X7 and P2Y11 receptors had no effects on Th17 and Th1 cell activation. Finally, treatment with the P2X4 receptor antagonist 5-BDBD reduced the severity of collagen-induced arthritis in mice by inhibiting Th17 cell expansion and activation. Our findings provide novel insights into the role of purinergic signaling in T cell activation and identify a critical role for the purinergic receptor P2X4 in Th17 activation and in autoimmune arthritis.

Metabolism Characteristics of Th17 and Regulatory T Cells in Autoimmune Diseases.

The abnormal number and functional deficiency of immune cells are the pathological basis of various diseases. Recent years, the imbalance of Th17/regulatory T (Treg) cell underlies the occurrence and development of inflammation in autoimmune diseases (AID). Currently, studies have shown that material and energy metabolism is essential for maintaining cell survival and normal functions and the altered metabolic state of immune cells exists in a variety of AID. This review summarizes the biology and functions of Th17 and Treg cells in AID, with emphasis on the advances of the roles and regulatory mechanisms of energy metabolism in activation, differentiation and physiological function of Th17 and Treg cells, which will facilitate to provide targets for the treatment of immune-mediated diseases.

Identification of Sorafenib as a Treatment for Type 1 Diabetes.

Th1 cell activation is considered a key mediator of the pathogenesis of type 1 diabetes. Targeting IL-12-induced Th1 cell differentiation seems to be an effective way to block the development of type 1 diabetes. However, given the critical function of Th1 in the immune system, the potential side effects hinder the application of anti-Th1 therapy in the treatment of type 1 diabetes. To identify safe anti-Th1 treatment(s), we screened the FDA-approved tyrosine kinase inhibitor (TKI) drug library using an IL-12-induced Th1 differentiation cell model. We found that among the TKIs with little effect on T cell viability, sorafenib is the top contender for the inhibition of Th1 differentiation. Treatment of NOD mice with sorafenib significantly impeded the development of type 1 diabetes and ameliorated insulitis, which coincided with a specifically decreased accumulation of Th1 cell population in the pancreas but not in peripheral immune organs. Mechanistically, sorafenib indirectly inhibited janus kinase 2 (JAK2) activity and blocked IL-12-induced phosphorylations of JAK2 and signal transducer and activator of transcription 4 (STAT4). Since sorafenib is classified as an FDA-approved drug, it serves as a preliminary lead point for additional experimentation and may be a promising therapy for type 1 diabetes in humans.

IL-17 Receptor Signaling through IL-17A or IL-17F Is Sufficient to Maintain Innate Response and Control of Helicobacter pylori Immunopathogenesis.

IL-17R signaling is required for control of extracellular pathogens and is also implicated in development of chronic inflammatory processes. The response to the human pathogen Helicobacter pylori results in Th1 and Th17 cell activation and a chronic inflammatory process that can lead to adverse outcomes, such as gastric cancer. Previously, we identified IL-17RA as a requirement for the recruitment of neutrophils and control of H. pylori colonization in the gastric mucosa. Unexpectedly, H. pylori-infected Il17ra -/- mice had significantly more chronic inflammation than H. pylori-infected wild-type mice. In this study, human epithelial cell lines and murine models were used to investigate differential roles for IL-17A, IL-17F, and IL-17A/F during H. pylori infection. Moreover, the hypothesis that IL-17RA signaling, specifically in lymphocytes, provides an autocrine feedback loop that downregulates Th17 cytokine production was investigated. The data indicate that epithelial cells exhibit a stronger response to IL-17A and IL-17A/F than IL-17F, and that IL-17A and IL-17A/F can synergize with TNF and IL-22 to induce antimicrobial genes of gastric epithelial cells. In vivo deficiencies of IL-17A or IL-17F alone did not significantly change the immunopathological response to H. pylori, but if both cytokines were absent, a hyperinflammatory lymphocytic response developed. Using a cre/flox targeting approach for IL-17RA combined with infection, our findings demonstrate that increased chronic inflammation in Il17ra -/- mice was not attributed to a T cell-intrinsic defect. These data imply that IL-17A and IL-17F may have overlapping roles in maintenance of the gastric mucosal response to infection.

JAK1 signaling in dendritic cells promotes peripheral tolerance in autoimmunity through PD-L1-mediated regulatory Tcell induction.

Dendritic cells (DCs) induce peripheral Tcell tolerance, but cell-intrinsic signaling cascades governing their stable tolerogenesis remain poorly defined. Janus Kinase 1 (JAK1) transduces cytokine-receptor signaling, and JAK inhibitors (Jakinibs), including JAK1-specific filgotinib, break inflammatory cycles in autoimmunity. Here, we report in heterogeneous DC populations of multiple secondary lymphoid organs that JAK1 promotes peripheral Tcell tolerance during experimental autoimmune encephalomyelitis (EAE). Mice harboring DC-specific JAK1 deletion exhibit elevated peripheral CD4+ Tcell expansion, less regulatory Tcells (Tregs), and worse EAE outcomes, whereas adoptive DC transfer ameliorates EAE pathogenesis by inducing peripheral Tregs, programmed cell death ligand 1 (PD-L1) dependently. This tolerogenic program is substantially reduced upon the transfer of JAK1-deficient DCs. DC-intrinsic IFN-γ-JAK1-STAT1 signaling induces PD-L1, which is required for DCs to convert CD4+ Tcells into Tregs invitro and attenuated upon JAK1 deficiency and filgotinib treatment. Thus, DC-intrinsic JAK1 promotes peripheral tolerance, suggesting potential unwarranted DC-mediated effects of Jakinibs in autoimmune diseases.

Inhibition of microRNA-448 suppresses CD4+ T cell inflammatory activation via up-regulating suppressor of cytokine signaling 5 in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. MicroRNA-448 (miR-448) has a pro-inflammatory effect in various inflammation-related diseases and is up-regulated in serum of patients with SLE. However, the role of miR-448 in SLE development remains elusive. In our study, we found high expression of miR-448 in peripheral blood mononuclear cells (PBMCs) of SLE patients, and miR-448 level was positively associated with disease severity. Besides, miR-448 level was up-regulated during the growth of MRL/lpr mice. To investigate the function of miR-448 in SLE, we subjected 8-week MRL/lpr mice to injection of lentivirus (LV)-mediated anti-miR-448. Inhibition of miR-448 reduced serum IgG and anti-dsDNA IgG contents, 24 h urine protein and blood urea nitrogen (BUN) levels, increased complement C3 concentration, and ameliorated splenomegaly and lymphadenectasis in MRL/lpr mice. MiR-448 inhibition alleviated renal inflammatory infiltration and glycogen deposition. Moreover, miR-448 inhibition promoted Treg cell activation and inhibited Th17 cell proportion in naïve CD4+ T cells from spleens, along with elevated interleukin (IL)-10 and reduced IL-17A levels. In vitro, miR-448 inhibition diminished CD4+ T cell polarization toward Th17 cells under Th17-polarizing conditions. Further, luciferase reporter assay revealed that miR-448 binds to the 3′UTR of suppressor of cytokine signaling 5 (SOCS5). SOCS5 expression was down-regulated in the spleens of MRL/lpr mice and induced Th17 cells. SOCS5 deficiency partially reversed the role of miR-448 in Th17 differentiation and IL-17A expression in SLE. Taken together, inhibition of miR-448 impedes Th17 cell activation and tissue damages via targeting SOCS5 in SLE.

TNFAIP8 modulates the survival and immune activity of Th17 cells via p53/ p21/ MDM2 pathway after acute insult

Th17 cells induced immunosuppression plays a vital role in sepsis. As a member of the tumor necrosis factor α induced protein 8 (TNFAIP8) family, TNFAIP8 is associated with different physiopathological conditions with immunological responses. However, its potential roles in regulating Th17 cells after the acute insult have not been fully elucidated. In this study, sepsis was induced by cecal ligation and puncture (CLP) in the male adult C57BL/6 mice. The stable TNFAIP8 knockdown (KD) Th17 cells were established by infecting with lentivirus carrying TNFAIP8-specific shRNA. CCK-8 assay was conducted to evaluate Th17 cell proliferation, and Annexin V/7-AAD assay was applied for apoptosis measurement by flow cytometry. The alterations of p53/ p21/ MDM2 pathway were assessed by Western blot. We observed that a high TNFAIP8 expression level was related to acute injury in septic mice. TNFAIP8 silencing suppressed Th17 cell proliferation and cytokine production in vivo and in vitro. In addition, TNFAIP8 KD increased Th17 cell apoptosis in septic mice. Furthermore, TNFAIP8 seems to affect the immune function of Th17 cells by regulating p53/ p21/ MDM2 signaling processes. We found that TNFAIP8 KD caused the up-regulation of P21 and MDM2, and also elevated p53 protein level during sepsis. Pharmacological inhibition of p53 partially rescued cell proliferation and apoptotic effects of TNFAIP8 KD. In summary, our work suggests that TNFAIP8 modulates the survival and immune function of Th17 cells after acute insult, which was possibly mediated through the p53/ p21/ MDM2 pathway.

Interleukin-33 as a Potential Diagnostic and Prognostic Factor in Human Brucellosis.

The balance between T-helper 1 (Th1) and T-helper 2 (Th2) cells plays an important role in the pathogenesis of brucellosis. Interleukin (IL)-33 induces the activation of Th2 cells while soluble suppression of tumorigenicity 2 (sST2) is a decoy receptor to antagonize the effect of IL-33. Herein, we aimed to identify whether plasma IL-33/sST2 levels could reflect the state of brucellosis and help to monitor the treatment. A total of 78 patients were recruited and divided into acute, subacute, and chronic groups. The chronic group was further divided into chronic active brucellosis and chronic stable brucellosis according to the clinical manifestation. Twenty-six volunteers were assigned to the healthy control (HC) group. Plasma IL-33/sST2 levels were detected by enzyme linked immunosorbent assay (ELISA) and other routine laboratory parameters were obtained from the clinical central laboratory. The level of IL-33 in acute (49.48 ± 18.92), subacute (41.35 ± 17.12), chronic active (44.99 ± 16.80), and the chronic stable (28.92 ± 13.12) groups were higher than that in the HC group (11.66 ± 3.26) (p < 0.001). The IL-33 level in the acute group decreased significantly after treatment (49.48 ± 18.92 vs. 29.89 ± 12.92) (p < 0.001). Furthermore, the IL-33 level in the chronic active group (44.99 ± 16.80) was higher than that in the chronic stable group (28.92 ± 13.12) (p < 0.01). Interestingly, IL-33 correlated with white blood cells (WBC) (r = 0.268, p < 0.05) and C-reactive protein (CRP) (r = 0.272, p < 0.05). The level of sST2 increased in the acute (3,717.76 ± 2,036.25), subacute (3,130.41 ± 1,931.71), chronic active (3,381.43 ± 1,394.83), and the chronic stable group (2,707.03 ± 1,260.26) groups compared with the HC group (297.76 ± 290.93) (p < 0.001). However, the sST2 plasma level showed no differences among the groups and did not significantly change after treatment in the acute group. IL-33 can reflect the state of brucellosis and may be a potential biomarker for diagnosis and monitoring treatment for brucellosis.

Гнездная алопеция у больных атопическим дерматитом: совпадение или закономерность?

Extensive trials have identified a close relationship between atopic dermatitis (AD) and alopecia areata (AA). This review paper summarizes and analyzes available data on the immunological pattern of AD-associated AA. The analysis of scientific findings suggests that epidermal barrier dysfunction in AD promotes AA in the presence of target genes contributing to its development. Both pathological entities negatively affect each other. The results are the reduction in regulatory T cell (Treg) suppression activity and an increase in inflammatory and autoimmune activity of Th-17 cells. Hyperergic Th2 response affects AD-associated AA clinical presentations. The regression of bald patches after IL-4, IL-13, and histamine receptors blockage further establishes the association between AA and AD. The possibility of atopic alopecia requires both skin and hair care products in AD. Dry peeling skin vulnerable to infections should be treated to reduce the risk of autoimmunity in AA. The presence of two family lines of genetic predisposition (atopy and AA) results in severe combined manifestations of these disorders in progeny. Therefore, attention should be paid to early AD signs in children in these families to commence treatment timely. KEYWORDS: atopic dermatitis, аlopecia areata, genetics, autoimmunity, epidermal barrier, regulatory T cells, immune privilege, hair follicle, T helper 17 cells, mast cells. FOR CITATION: Petrova S.Yu., Albanova V.I. Alopecia areata in atopic dermatitis: coincidence or regularity? Russian Medical Inquiry. 2022;6(2):85–91 (in Russ.). DOI: 10.32364/2587-6821-2022-6-2-85-91.

Multiple sclerosis and allergic diseases: is there a relationship?

&lt;abstract&gt; &lt;p&gt;Immune system disorders characterize various diseases such as multiple sclerosis (MS) and allergic diseases (AD). In MS, T-helper (Th)1 cell phenotype is responsible for the disease onset and long-term evolution. On the other hand, excessive Th2 cell activity has been demonstrated in AD. The simultaneous increase of MS and AD in the same geographical areas, observed in recent years, has questioned the mutually exclusive correlation between MS and AD immunopathogenesis supported by the Th1/Th2 paradigm and has moved the interest in understanding possible overlaps. This manuscript aims to discuss the literature, collected over the past two decades, about the association between MS and AD, and both experimental and epidemiological studies have been reviewed. The results do not provide a solid correlation between AD and MS, although experimental studies support the involvement of the same cells and molecules in the immunopathogenesis of both diseases. Further studies, increasing knowledge on the cellular and molecular mechanisms involved in these two disorders, could help to clarify if a positive or negative association links them and provide the possibility for the development of new therapies.&lt;/p&gt; &lt;/abstract&gt;

Efficacy and safety of guselkumab and adalimumab for pustulotic arthro-osteitis and their impact on peripheral blood immunophenotypes

ObjectivesWe compared the treatment effectiveness between guselkumab and adalimumab in patients with pustulotic arthro-osteitis (PAO). In addition, we performed peripheral blood immunophenotyping to elucidate the immunological background and analyzed the impact of therapeutic drugs to verify the validity of immunological phenotypes as therapeutic targets.MethodsPatients were treated with guselkumab 100 mg (guselkumab group; n = 12) and adalimumab 40 mg (adalimumab group; n = 13). Arthritis disease activity, skin lesion activity, and patient-reported outcomes (PROs) were evaluated and compared between the two groups. The retention rate and adverse events were evaluated. Comprehensive phenotyping of peripheral immune cells was performed in both groups, and phenotypes were compared before and after treatment.ResultsAt 6 months, both groups showed significant improvement in arthritis disease activity and PROs. In the guselkumab group, skin symptoms significantly improved. The 6-month continuation rates were 91.7% (11/12) and 69.2% (9/13) in the guselkumab and adalimumab groups, respectively. Adverse events occurred in 2/12 and 5/13 patients in the guselkumab (16.7%) and adalimumab (38.5%) groups, respectively. Peripheral blood immunophenotyping showed that the proportion of activated T helper (Th) 1 cells was significantly lower in patients with PAO than in healthy controls and that the proportion of activated Th17 cells was significantly higher in patients with PAO, which significantly decreased after treatment with guselkumab.ConclusionAlthough guselkumab and adalimumab have comparable efficacy for PAO, their impact on immunophenotypes varies.

The Immuno-Modulatory Activities of Pentaherbs Formula on Ovalbumin-Induced Allergic Rhinitis Mice via the Activation of Th1 and Treg Cells and Inhibition of Th2 and Th17 Cells.

Allergic rhinitis (AR) is a highly prevalent allergic disease induced by immunoglobulin (Ig) E-mediated hypersensitivity reaction at the nasal epithelium against inhaled allergens. Previous studies have demonstrated that Pentaherbs formula (PHF), a modified herbal formula comprising five herbal medicines (Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis), could suppress various immune effector cells to exert anti-inflammatory and anti-allergic effects in allergic asthma and atopic dermatitis. The present study aimed to further determine the anti-inflammatory activities of PHF in an ovalbumin (OVA)-induced AR BALB/c mouse model. Nasal symptoms such as sneezing and nose rubbing were recorded and the serum total IgE and OVA-specific IgG1, as well as interleukin (IL)-4, IL-5, IL-10, IL-13, chemokines CXCL9 CXCL10, and tumor necrosis factor (TNF)-α concentrations in nasal lavage fluid (NALF) were measured during different treatments. Effects of PHF on the expression of inflammatory mediators in the sinonasal mucosa were quantified using real-time QPCR. PHF was found to suppress allergic symptoms, infiltration of inflammatory cells, and hyperplasia of goblet cells in the nasal epithelium of the OVA-induced AR mice. PHF could reduce OVA-specific IgG1 level in serum, and TNF-α and IL-10 in nasal lavage fluid (NALF), significantly up-regulate the splenic regulatory T (Treg) cell level, increase the Type 1 helper T cell (Th1)/Type 2 helper T cell (Th2) ratio, and reduce the Th17 cells (all p < 0.05). PHF could also alleviate in situ inflammation in sinonasal mucosa of OVA-induced AR mice. In conclusion, oral treatment of PHF showed immuno-modulatory activities in the OVA-induced AR mice by regulating the splenic T cell population to suppress the nasal allergy symptoms and modulating inflammatory mediators, implicating that PHF could be a therapeutic strategy for allergic rhinitis.

IL-17-induced hypertension results in placental mitochondrial dysfunction and fetal growth restriction independent of T cells

Preeclampsia (PE), new onset hypertension (HTN) during pregnancy, is associated with fetal growth restriction (FGR), multi-organ dysfunction, increased Natural Killer cells, T helper cells, and interleukin 17 (IL-17). We have shown that IL-17 stimulates TH17 cells and NK cells in association with placental mitochondrial (mt) dysfunction, FGR and HTN in pregnant Sprague Dawley rats. However, our previous studies have not differentiated the effects of activated TH cells verses IL-17. The athymic nude rat lacks T cells but does have other components of the immune system, allowing us to examine the role of IL-17 in the absence of T cells in the pathophysiology of PE.

Sacran polysaccharide improves atopic dermatitis through inhibiting Th2 type immune response

AimsThis study was aimed to explore whether sacran polysaccharide has a therapeutic effect on atopic dermatitis (AD) and its possible mechanisms. Materials and methods2, 4-dinitrochlorobenzene (DNCB)-induced AD mice were treated with 0.2% Sacran, 0.5% Sacran and 0.1% tacrolimus. Through scoring dermatitis severity, measuring ear thickness, cracking behavior, open field test, we evaluated the therapeutic effect of Sacran on DNCB-induced AD mice. CD4+ T cells and CD8+ T cells were evaluated by flow cytometry. The relative expression of Ifng and Il4 were measured by real-time quantitative PCR. Key findingsSacran could relieved the symptoms of DNCB-induced AD mice, such as AD score, ear thickness, and IgE release. Sacran may alleviate dermatitis by inhibiting Th2 activation and reducing IgE release. SignificanceOur research further proved that polysaccharide Sacran has anti-dermatitis effects, and also clarified its mechanism of alleviating dermatitis by inhibiting the activation of Th2 cells and reducing the release of IgE, which provides a theoretical basis for the future clinical transformation of polysaccharide Sacran.

Recurrence of alopecia areata after covid‐19 vaccination: A report of three cases in Italy

Common COVID-19 vaccines side effects are pain at the injection site, muscle pain, fever, headaches, fatigue. Possible immune-related side effects in predisposed individuals have not been established so far. We report three cases of recurrence of alopecia areata (AA) occurred after the first dose of COVID-19 vaccine. All patients had previous episodes of AA with total hair regrowth and stable remission during the months preceding the vaccination. Rapid hair loss occurred 2-3 weeks after BNT162b2 mRNA (patient 1) and AZD1222/ChAdOx1 vaccine (patient 2 and 3), with widespread hair loss in two cases and a single patch of the vertex in one case, with typical trichoscopic features of AA. Both BNT162b2 mRNA and AZD1222/ChAdOx1 vaccines share the same goal of inducing the immune system, with antibodies production and Th1 cells activation with release of pro-inflammatory cytokines. Thus, in patients with pre-existing inflammatory dysregulated pathways, the interaction between the immune system and vaccines may enhance other autoimmune mechanisms. In our cases, we speculate that vaccine may have induced the hair loss focusing on components having a key role in both COVID-19 vaccination and AA pathogenesis. This report may help to collect new data concerning possible immune-related effects of vaccines. Certainly, only three cases are not sufficient to draw conclusion, thus a large-scale study is necessary. Immune-mediated side effects remain a rare event, thus the benefits of COVID-19 vaccines outweigh the risk of disease flares and we strongly recommend it in all eligible patients with AA.