Adaptive Immune Responses Research Articles

Computational Analysis of T-Cell Receptor Repertoire Workflow: From T-Cell Isolation to Bioinformatics Analysis.

The T-cell receptor (TCR) is the key molecule involved in the adaptive immune response. It is generated by the V(D)J recombination, responsible of the enormous diversity of the TCR repertoire, a crucial feature determining the individual capability to response to antigens and to build immunological memory. A pivotal role in the recognition of antigen is played by the hypervariable complementarity-determining region 3 (CDR3) of the V-beta chain of TCR. Investigating the CDR3 supports the understanding of the adaptive immune system dynamics in physiological processes, such as immune aging, and in disease, especially autoimmune disorders in which T cells are main actors. High-throughput sequencing (HTS) paved the way for a great progress in the investigation of TCR repertoire, enhancing the read depth in the process of library generation of sequencing and the number of samples that can be analyzed simultaneously. Therefore, the leverage of big datasets stressed the need to develop computational approach, by bioinformatics, to unravel the characteristics of the TCR repertoire.

Paracetamol suppresses neutrophilic oxygen radicals through competitive inhibition and scavenging

Neutrophils, pivotal cells of innate and adaptive immune responses, employ reactive oxygen species (ROS) to combat pathogens and control gene expression. Paracetamol (acetaminophen) is widely used as an analgesic and antipyretic medication, yet its precise mechanisms of action are not yet fully understood. Here, we investigate the impact of both ingested and in-vitro paracetamol on neutrophil ROS activity, using flow cytometry and antioxidant assays. Our studies reveal that paracetamol significantly suppresses ROS activity ex-vivo in the short term. Additionally, both paracetamol and its metabolite N-acetyl-p-benzoquinone imine exhibited direct in vitro antioxidant effects, and paracetamol suppressed neutrophil extracellular trap formation ex vivo. These findings suggest a connection between paracetamol use and altered neutrophil responses, with potential implications for use in some patient groups, such as immunocompromised individuals. Further investigation into paracetamol's effects on neutrophil antimicrobial functions is warranted to elucidate possible risks, particularly when taken frequently or in conjunction with other treatments such as vaccinations.

Effects of immunosuppression after limb fracture in mice on nociceptive, cognitive, and anxiety-related outcomes.

Chronic pain is a common and problematic consequence of injuries with few proven methods for prevention or treatment. In addition to pain, functional limitations and neuropsychiatric changes such as cognitive impairment and anxiety worsen outcomes. To determine whether inhibiting activation of the adaptive immune response after limb fracture would reduce pain, functional loss, memory changes, and anxiety. These experiments used a murine tibial fracture/cast immobilization model that develops these adverse outcomes. Adaptive immunity was blocked using the immunosuppressant FK506 beginning at the time of fracture. The administration of FK506 reduced mechanical allodynia and hind limb unweighting for weeks after cast removal as well as nonevoked pain measures. Fracture was associated with working memory loss in the Y-maze assay in vehicle- but not FK506-treated mice. Object recognition memory was not improved with FK506 after fracture. Also, vehicle- but not FK506-treated mice developed an anxiety phenotype. Impaired running wheel performance after cast removal over the following 2 weeks was not improved with FK506 administration. In addition, FK506 treatment blocked Immunoglobulin M (IgM) accumulation in the skin of the fractured limbs, and hippocampal enhancement of matrix metalloproteinase-8 expression, a metalloproteinase associated with neuroplastic changes after injuries, was completely blocked. Taken together, our results show that blocking the adaptive immune response after limb trauma reduces the severity of nociceptive and biological changes. The same treatment may reduce the adverse consequences of anxiety and memory deficits using some measures, but other measures of memory are not affected, and activity is not enhanced.

Inflammatory Myopathies and Autoimmune Gluten-related Disorders: A Scoping Review of Pathophysiological Interconnections and Hypothesis

Introduction: Anecdotal reports describe patients with concurrent idiopathic inflammatory myopathy (IIM) and celiac disease (CeD) in whom the introduction of a gluten-free diet led to dramatic improvement of myositis. We first systematically reviewed all peer-reviewed publications on concomitant IIM and duodenal biopsy-verified CeD. The collected evidence was suggestive of associations between myositis disease activity and gluten exposure in some patients with IIM-CeD. Objective/Methods: To investigate possible explanations for the observations, an exploratory review of basic pathophysiological relationships between IIM and gluten-related disorders was performed using a combined strategy of systematic and non-systematic literature searches and forward and backward citation tracking. Results: The investigations revealed close pathophysiological associations between IIM and the autoimmune gluten-related disorders CeD, dermatitis herpetiformis, and gluten ataxia. Common traits include shared genetic predisposition through HLA-DQ2.5/-DQ8, disease activity-associated autoantibodies, histopathological parallels with inflammatory cell infiltrates, and similarly distributed structural homologous transglutaminases (TGs). HLA-DQ2.5-restricted gluten-specific CD4+ T cells of a rare, uniform phenotype are reported in CeD and connective tissue disease. Expanded T-cell clones with identical phenotypes and CDR3β motifs indicate the presence of a continuous, antigen-driven T-cell response. Conclusion: The investigations revealed that the main components involved in the adaptive immune response in the CeD gut may be present in HLA-DQ2.5+/-DQ8+ IIM muscle. The collected evidence supports the notion that in some genetically predisposed patients with IIM, gluten may act as an exogenous antigen driving myositis. Further Research/Clinical Implications: To test the above hypothesis, clinical trials combined with immunological studies are needed. Meanwhile, the inclusion of HLA-DQ typing may be justified, and subsequent small-intestinal biopsies in HLA-DQ2.5/8+ individuals with IIM.

Host genetic diversity and body condition influence parasite resistance and clearance in a wild marine mammal population.

Host genetic variability can modulate infection resistance, although its role in infection clearance remains unclear. Hookworm disease (Uncinaria sp.) is the leading cause of pup mortality in several otariid species, although the parasite can be cleared through immune-mediated processes. We evaluated the association of host genetic diversity, body condition and immune response with hookworm resistance and/or clearance in the South American fur seal (Arctocephalus australis). Uninfected pups had higher heterozygosity than parasitized individuals, indicating a negative relationship between heterozygosity and the chances of infection. Likewise, pups that died of hookworm infection had lower heterozygosity than those that died of non-infectious causes. Interestingly, once infected, pups that survived hookworm infection had heterozygosities similar to pups that died of hookworm disease. However, pups that cleared the infection had a higher body mass and parasite-specific immunoglobulin G levels than those that did not recover or died of hookworm disease. Thus, although heterozygosity predicted resistance to and mortality from hookworm infections, it did not affect parasite clearance, which was facilitated by better body condition and adaptive immune responses. This demonstrates that host genetic variability and host-environment interactions influence disease dynamics, acting at different, well-defined stages of infection.

Non-RBD peptides of SARS-CoV-2 spike protein exhibit immunodominance as they elicit both innate and adaptive immune responses

Non-RBD peptides of SARS-CoV-2 spike protein exhibit immunodominance as they elicit both innate and adaptive immune responses

Rebalancing immune homeostasis in combating disease: the impact of medicine food homology plants and gut microbiome

BackgroundGut microbiota plays an important role in multiple human physiological processes and an imbalance in it, including the species, abundance, and metabolites can lead to diseases. These enteric microorganisms modulate immune homeostasis by presenting a myriad of antigenic determinants and microbial metabolites. Medicinal and food homologous (MFH) plants, edible herbal materials for both medicine and food, are important parts of Traditional Chinese Medicine (TCM). MFH plants have drawn much attention due to their strong biological activity and low toxicity. However, the interplay of MFH and gut microbiota in rebalancing the immune homeostasis in combating diseases needs systematic illumination. PurposeThe review discusses the interaction between MFH and gut microbiota, including the effect of MFH on the major group of gut microbiota and the metabolic effect of gut microbiota on MFH. Moreover, how gut microbiota influences the immune system in terms of innate and adaptive immunity is addressed. Finally, the immunoregulatory mechanisms of MFH in regulation of host pathophysiology via gut microbiota are summarized. MethodsLiterature was searched, analyzed, and collected using databases, including PubMed, Web of Science, and Google Scholar using relevant keywords. The obtained articles were screened and summarized by the research content of MFH and gut microbiota in immune regulation. ResultsThe review demonstrates the interaction between MFH and gut microbiota in disease prevention and treatment. Not only do the intestinal microorganisms and intestinal mucosa constitute an important immune barrier of the human body, but also lymphoid tissue and diffused immune cells within the mucosa participate in the response of innate immunity and adaptive immunity. MFH modulates immune regulation by affecting intestinal flora, helps maintain the balance of the immune system and interfere with the occurrence and development of a broad category of diseases. ConclusionBeing absorbed from the gastrointestinal tract, MFH can have profound effects on gut microbiota. In turn, the gut microbiota also actively participate in the bioconversion of complex constituents from MFH, which could further influence their physiological and pharmacological properties. The review deepens the understanding of the relationship among MFH, gut microbiota, immune system, and human diseases and further promotes the progression of additional relevant research.

Application of immunoinformatics to develop a novel and effective multiepitope chimeric vaccine against Variovorax durovernensis

Bloodstream infections pose a significant public health challenge caused by resistant bacteria such as Variovorax durovernensis, a recently reported Gram-negative bacterium, worsening the burden on healthcare systems. The design of a vaccine using chimeric peptides derived from a representative V. durovernensis strain holds significant promise for preventing disease onset. The current study aimed to employ reverse vaccinology (RV) approaches such as the retrieval of V. durovernensis proteomics data, removal of redundant proteins by CD-HIT, filtering of non-homologous proteins to humans and essential proteins, identification of outer membrane (OM) proteins by CELLO and PSORTb. Following these steps immunoinformatic approaches were applied, such as epitope prediction by IEDB, vaccine design using linkers and adjuvant andanalysis of antigenicity, allergenicity, safety and stability. Among the 4208 nonredundant proteins, an OmpA family protein (A0A940EKP4) was designated a potential candidate for the development of a multiepitope vaccine construct. Upon analysis of OM protein, six immunodominant (B cell) epitopes were found on the basis of the chimeric construct following the prediction of CTL stands cytotoxic T lymphocyte and HTL stands helper T lymphocyte epitopes. To ensure comprehensive population coverage globally, the CTL and HTL coverage rates were 58.18% and 46.56%, respectively, and 77.23% overall. By utilizing EAAAK, GPGPG, and AAY linkers, Cholera toxin B subunit adjuvants, and appropriate epitopes were smoothly incorporated into a chimeric vaccine effectively triggering both adaptive and innate immune responses. For example, the administered antigen showed a peak in counts on the fifthday post injection and then gradually declined until the fifteenth day. Elevated levels of several antibodies (IgG + IgM > 700,000; IgM > 600,000; IgG1 + IgG2; IgG1 > 500,000) were observed as decreased in the antigen concentration. Molecular dynamics simulations carried out via iMODS revealed strong correlations between residue pairs, highlighting the stability of the docked complex. The designed vaccine has promising potential in eliciting specific immunogenic responses, thereby facilitating future research for vaccine development against V. durovernensis.

Dinámica de los receptores de quimioquinas en la membrana celular

Chemokines are chemotactic cytokines that control the migratory patterns and positioning of many cells, including immune cells. Although chemokines were initially considered to be important mediators of acute inflammation, we now know that this complex system of ligands and receptors is essential for the generation of primary and secondary adaptive cellular and humoral immune responses. In addition, they also trigger other biological responses ranging from cell polarization or movement or the prevention of HIV-1 infection. Chemokine-mediated cell activation was believed to be due to the binding of a monomeric chemokine to its monomeric receptor. However, the biology of these mediators is more complex than initially anticipated, as several studies indicate that chemokines dimerize. In addition, the use of new advanced optical imaging techniques have made possible to determine that the receptors also form dimers, homo- and heterodimers, as well as higher order oligomers at the cell surface. These are very dynamic and plastic structures/conformations, influenced by the presence of ligands, the co-expression of other receptors and proteins, the lipid composition of the cell membrane or the environment where cells perform their function. Keywords: Chemokines; Chemokine receptors; Receptor conformation; Molecular dynamics; Signaling

A Multifunctional Biomimetic Nanoplatform for Dual Tumor Targeting-Assisted Multimodal Therapy of Colon Cancer.

The biomimetic nanoparticles (NPs) possessing abilities of tumor targeting and multimodal therapy show great potential for efficient combat of colon cancer. Herein, we developed a multifunctional biomimetic nanoplatform (Fe3O4@PDA@CaCO3-ICG@CM) based on CaCO3-modified magnetic polydopamine (PDA) loaded with indocyanine green (ICG), which was encapsulated by a mouse lymphoma cell (EL4) membrane (CM) expressing functional proteins (i.e., lymphocyte function-associated antigen 1, LFA-1; transforming growth factor-β receptor, TGF-βR; programmed cell death protein 1, PD-1; and factor related apoptosis ligand, FasL). Under magnetic attraction and LFA-1/PD-1-mediated endocytosis, Fe3O4@PDA@CaCO3-ICG@CM efficiently targeted CT26 colon tumor cells. The released calcium ion (Ca2+) from the NPs triggered by acidic tumor microenvironment, the enhanced photothermal effect contributed by the combination of PDA and ICG, and FasL's direct killing effect together induced tumor cells apoptosis. Moreover, the apoptosis of CT26 cells induced immunogenic cell death (ICD) to promote the maturation of dendritic cells (DCs) to activate CD4+/CD8+ T cells, thereby fighting against tumor cells, which could further be boosted by programmed death-ligand 1 (PD-L1) blockage and transforming growth factor-β (TGF-β) scavenging by Fe3O4@PDA@CaCO3-ICG@CM. As a result, in vivo satisfactory therapeutic effect was observed for CT26 tumor bearing-mice treated with Fe3O4@PDA@CaCO3-ICG@CM under laser irradiation and magnetic attraction, which could eradicate primary tumors and restrain distant tumors through dual tumor targeting-assisted multimodal therapy and eliciting adaptive antitumor immune response, generating the immune memory for inhibiting tumor metastasis and recurrence. Taken together, the multifunctional biomimetic nanoplatform exhibits superior antitumor effects, providing an insightful strategy for the field of nanomaterial-based treatment of cancer.

TLR3/TRIF and MAVS Signaling Is Essential in Regulating Mucosal T Cell Responses during Rotavirus Infection.

The functions of the natural dsRNA sensors TLR3 (TRIF) and RIG-I (MAVS) are crucial during viral challenge and have not been accurately clarified in adaptive immune responses to rotavirus (RV) infection. In this study, we found that RV infection caused severe pathological damage to the small intestine of TLR3-/- and TRIF-/- mice. Our data found that dendritic cells from TLR3-/- and TRIF-/- mice had impaired Ag presentation to the RV and attenuated initiation of T cells upon viral infection. These attenuated functions resulted in impaired CD4+ T and CD8+ T function in mice lacking TLR3-TRIF signaling postinfection. Additionally, attenuated proliferative capacity of T cells from TLR3-/- and TRIF-/- mice was observed. Subsequently, we observed a significant reduction in the absolute number of memory T cells in the spleen and mesenteric lymph node (MLN) of TRIF-/- recipient mice following RV infection in a bone marrow chimeric model. Furthermore, there was reduced migration of type 2 classical dendritic cells from the intestine to MLNs after RV infection in TLR3-/- and TRIF-/- mice. Notably, RV infection resulted in attenuated killing of spleen and MLN tissues in TRIF-/- and MAVS-/- mice. Finally, we demonstrated that RV infection promoted apoptosis of CD8+ T cells in TRIF-/- and TLR3-/-MAVS-/- mice. Taken together, our findings highlight an important mechanism of TLR3 signaling through TRIF in mucosal T cell responses to RV and lay the foundation for the development of a novel vaccine.

Multi-Metallic Nanosheets Reshaping Immunosuppressive Tumor Microenvironment through Augmenting cGAS-STING Innate Activation and Adaptive Immune Responses for Cancer Immunotherapy.

The highly immunosuppressive tumor microenvironment (TME) restricts the efficient activation of immune responses. To restore the surveillance of the immune system for robust activation, vast efforts are devoted to normalizing the TME. Here, a manganese-doped layered double hydroxide (Mn-LDH) is developed for potent anti-tumor immunity by reversing TME. Mn-LDH is synthesized via a one-step hydrothermal method. In addition to the inherent proton neutralization capacity of LDH, the introduction of manganese oxide endows LDH with an additional ability to produce oxygen. Mn-LDH effectively releases Mn2+ and Mg2+ upon exposure to TME with high levels of H+ and H2O2, which activates synthase-stimulator of interferon genes pathway and maintains the cytotoxicity of CD8+ T cells respectively, achieving a cascade-like role in innate and adaptive immunity. The locally administered Mn-LDH facilitated a "hot" network consisting of mature dendritic cells, M1-phenotype macrophages, as well as cytotoxic and helper T cells, significantly inhibiting the growth of primary and distal tumors. Moreover, the photothermal conversion capacity of Mn-LDH sparks more robust therapeutic effects in large established tumor models with a single administration and irradiation. Overall, this study guides the rational design of TME-modulating immunotherapeutics for robust immune activation, providing a clinical candidate for next-generation cancer immunotherapy.

Molecular Signature Associated With Acute Rejection in Vascularized Composite Allotransplantation.

A deeper understanding of acute rejection in vascularized composite allotransplantation is paramount for expanding its utility and longevity. There remains a need to develop more precise and accurate tools for diagnosis and prognosis of these allografts, as well as alternatives to traditional immunosuppressive regimens. Twenty-seven skin biopsies collected from 3 vascularized composite allotransplantation recipients, consisting of face and hand transplants, were evaluated by histology, immunohistochemistry staining, and gene expression profiling. Biopsies with clinical signs and symptoms of rejection, irrespective of histopathological grading, were significantly enriched for genes contributing to the adaptive immune response, innate immune response, and lymphocyte activation. Inflammation episodes exhibited significant fold change correlations between the face and hands, as well as across patients. Immune checkpoint genes were upregulated during periods of inflammation that necessitated treatment. A gene signature consisting of CCL5, CD8A, KLRK1, and IFNγ significantly predicted inflammation specific to vascularized composite allografts that required therapeutic intervention. The mechanism of vascularized composite allograft-specific inflammation and rejection appears to be conserved across different patients and skin on different anatomical sites. A concise gene signature can be utilized to ascertain graft status along with a continuous scale, providing valuable diagnostic and prognostic information to supplement current gold standards of graft evaluation.

Flagellate bacteria-mediated tumour antigen delivery: A novel approach to enhance dendritic cell activation for insitu cancer vaccination.

In situ vaccination is a therapeutic approach aimed at exploiting tumour antigens available at a tumour site to induce tumour-specific adaptive immune responses. Antigens released from dying tumour cells are assumed to be taken up by activated dendritic cells and presented to T cells that seek out and destroy tumour cells. This process is significantly impeded in the immunosuppressive microenvironment of tumours. There is a growing trend in insitu vaccine strategies that utilize bacteria as natural adjuvants or as factories for cytokines, aiming to enhance the presentation of insitu antigens by antigen-presenting cells. Recently, a novel approach using flagellate bacteria-mediated antigen delivery to activate dendritic cells has been proposed. This method actively facilitates the delivery of intratumoral antigens, improving their presentation for insitu cancer vaccination. Here, we highlight how flagellate bacteria-mediated antigen delivery enhances the immune activation capabilities of insitu vaccines. Meanwhile, we provide perspectives and outlooks on these promising antigen delivery technologies.

Hyperfunctional T cell responses unchecked by regulatory T cells are unable to resolve hepaciviral infection without humoral contribution

Background & AimsThe most recent T cell-based vaccine against hepatitis C virus (HCV) in human subjects failed to swing the pendulum from chronicity to resolution despite eliciting cellular responses in the majority of individuals. These results naturally evoke the question of whether hyperactivated responses of a single adaptive immune arm are capable of inducing HCV clearance or if coordinated efforts between antibodies and T cells are indeed necessary. Here, we sought to address this point in determining whether the suppression of antiviral T cell and IgG responses by regulatory T cells (Tregs) is a critical prerequisite of delayed viral clearance or overt chronicity. MethodsUsing a surrogate model of HCV infection, rodent hepacivirus (RHV) infection in mice, we utilized Foxp3-DTR mice to assess how Tregs modulate the generation of acute antiviral adaptive immune responses and indirectly dictate infection fate via intracellular flow cytometry staining, ELISA, RNA sequencing, and qPCR. ResultsTransient depletion of Tregs prior to infection decreased viral-specific CD4+ T cell function, IgG production, and delayed viral clearance. In contrast, transient Treg depletion after infection increased both T cell functionality and IgG production, thereby facilitating accelerated viral clearance. Hyperactivated T cells, achieved via transient Treg depletion, were unable to clear the virus as an isolated effector arm without the help of viral-specific IgG production. ConclusionsTregs control the outcome of RHV infection via direct modulation of CD4+ T cells and IgG production. Hyperactivated T cell responses are incapable of compensating for experimentally induced lack of antibodies, further reinforcing the notion of cooperative interplay between adaptive immune arms in facilitating hepaciviral clearance. Impact and implicationsWe demonstrate herein how timing of Treg depletion determines the fate of effector T cells, humoral responses, and the kinetics of viral clearance. Our observations provide direct evidence that functional T cell responses are incapable of compensating for suboptimal humoral responses in facilitating viral resolution. Our results imply that future HCV vaccine regimens should not solely rely on eliciting focused responses of a single effector arm, but rather incorporate immunogens capable of inducing durable features of both humoral and cellular memory.

Interleukin-27 Regulates Adaptative Immune Responses Associated With Control of Parasite Replication in Canine Leishmaniasis.

Interleukin 27 (IL-27) is a cytokine that regulates susceptibility to Leishmania infantum infection in humans and experimental models. This cytokine has not yet been described in canine leishmaniasis (CanL). Therefore, we investigated whether IL-27 has a regulatory role in CanL. The EBI3 and p28 subunits of IL-27 were measured in splenic leukocytes culture supernatant from dogs with CanL and compared to control dogs. We also correlated EBI3 and p28 levels with IL-21, anti-L. infantum antibodies and parasite loads. We performed functional assays followed by IL-27 blockade and measured parasite loads, production of cytokines in splenic leukocytes culture supernatant, and the expression of PD-1, CTLA-4, phospho-Stat-1/3, T-bet, GATA3 and nitric oxide production (NO). Both IL-27 subunits increased in the supernatant of dogs with CanL compared to control dogs. EBI3 and p28 levels showed a moderate positive correlation with IL-21 (r = 0.67, p < 0.0001 and r = 0.45, p < 0.012, respectively), and the EBI3 subunit was positively associated with anti-L. infantum IgG antibodies (r = 0.38, p < 0.040) and parasite load (r = 0.47, p < 0.009). IL-27 and IL-21 participate of immune responses in CanL. IL-27 may be associated with the failure of immunity to control parasite replication via upregulation of the expression of PD-1, CTLA-4, T-bet and NO in splenic leukocytes from dogs with CanL. These findings suggest that the pathways regulated by IL-27 are involved in CanL pathogenesis in the host, and may be targets for new therapies.

In-vitro impacts of glyphosate on manatee lymphocytes

Exposure to contaminants, such as the herbicide glyphosate, can suppress protective immune functions. Glyphosate is the herbicide most used worldwide and has been found in plasma of more than 50 % of the Florida manatees and all-year-round in their aquatic environment. Our objectives were to analyze the consequences of glyphosate exposure on their immune responses via T-lymphocyte proliferation assays and transcriptomics. We isolated peripheral blood mononuclear cells (mainly lymphocytes) of free-ranging manatees and performed T-cell proliferation assays. We used transcriptomics to understand the consequences of glyphosate in vitro exposure. The 3 doses chosen ranged from environmentally relevant concentrations at 10 to 10,000 µg.L-1 that is considered a contamination scenario. Glyphosate caused a dose-dependent reduction in T-lymphocyte proliferation, with a significant mean reduction of 27.3 % at 10,000 µg.L-1 and up to 51.5 % in some individuals. Additionally, T-lymphocyte proliferation was significantly reduced in mid-winter compared to early winter. Transcriptomic analysis of peripheral blood mononuclear cells indicated that all doses of glyphosate (10, 1,000 and 10,000 µg.L-1) resulted in up-regulation of genes related to acute phase inflammation and inhibition of the T-lymphocyte proliferation pathway. Exposure to this contaminant along with other environmental stressors, such as extreme winters and red tide, might further affect the adaptive immune response of this threatened species.

Cytokine Signature Differences in Major Phenotypic Groups of Behçet Disease.

Behçet disease (BD) has heterogeneous presentations, mainly mucocutaneous, vascular, and ocular manifestations. The mechanisms associated with different phenotypes have not been clarified. We aimed to investigate the expression of innate and adaptive immunity-related cytokines in these 3 main BD phenotypes in active and untreated states and remission after treatment to be able to develop a cytokine-based treatment algorithm. Serum samples were isolated from 41 patients with newly diagnosed active BD (aBD), which consisted of 19 mucocutaneous aBD, 11 ocular aBD (o-aBD), and 11 vascular aBD patients, 35 patients in remission (rBD), and 9 healthy controls (HC). Serum levels of each cytokine were measured with sandwich enzyme-linked immunosorbent assay and analyzed as both raw measurements and corrected levels for each 1 million white blood cells. The study included 41 aBD patients (female/male [F/M]: 9/32; median age, 29 years), 35 rBD patients (F/M: 9/26; median age, 29 years), and 9 HC (F/M: 3/6; median age, 28 years). The serum interferon γ level was significantly higher in the aBD group than in the rBD (116 vs. 92 pg/mL, p = 0.022). The serum interleukin 35 (IL-35) level was significantly higher in the HC group compared with aBD and rBD (p = 0.05). IL-17-related cytokines were lower in o-aBD. With treatment, they increased in o-aBD but decreased in mucocutaneous aBD and vascular aBD patients. This study supports the involvement of both innate and TH1-predominated adaptive immune responses across all BD phenotypes. The IL-17 and TH17-related immune responses appear less prominent in ocular BD, which may explain the ineffectiveness of IL-17 blockade in treating ocular BD. These findings support the need for further studies using comprehensive gene expression analyses to develop targeted treatment strategies for BD phenotypes.

Female reproductive tract microbiota varies with MHC profile.

Numerous studies have shown that a healthy reproductive tract microbiota is crucial for successful reproduction and that its composition is influenced by various environmental and host factors. However, it is not known whether the reproductive microbiota is also shaped by the major histocompatibility complex (MHC), a family of genes essential to differentiate 'self' from 'non-self' peptides to initiate an adaptive immune response. We tested the association between the follicular fluid microbiome and MHC genes in 27 women. Women with higher MHC diversity had a higher microbiome diversity, characterized by bacteria commonly associated with vaginal dysbiosis. Women with similar MHC genes were also similar in their microbiome composition, indicating that MHC composition may be a key factor in determining the bacterial assemblage in the reproductive tract. Finally, the composition of the follicular fluid microbiome was similar to the vaginal microbiome, suggesting that numerous bacteria of the vagina are true inhabitants of the follicular fluid or that vaginal microbiota contaminated the follicular fluid microbiota during transvaginal collection. Collectively, our results demonstrate the importance of host genetic factors in shaping women's reproductive microbiota and they open the door for further research on the role of microbiota in mediating MHC-related variation in reproductive success.

Inflammation, tertiary lymphoid structures, and lung cancer: a bibliometric analysis.

The intricate interplay between inflammation and lung cancer has long been recognized by large number of studies, yet a comprehensive understanding of this relationship remains elusive. There is a clinical need to elucidate the role of tertiary lymphoid structures (TLSs) in lung cancer, particularly their impact on prognosis and therapy. This study aims to address these gaps by conducting a bibliometric analysis to explore the correlations between lung cancer, inflammation, and TLS, highlighting collaborative networks, publication trends, and emerging research directions. This study conducted a comprehensive bibliometric analysis of academic literature on lung cancer and inflammation from 2013 to 2023 using the Web of Science Core Collection database. The search strategy "topic (TS) = ('lung cancer') AND TS = (inflammation)" yielded 5,470 records, which were refined through exclusion criteria to 1,284 relevant studies. The inclusion process involved excluding non-English studies and non-original articles or reviews, followed by a relevance check based on titles and abstracts. The bibliometric indicators were calculated based on a transparent and repeatable methodology to ensure the integrity of the findings. The investigation encompassed 1,284 selected studies, revealing an escalating publication trend since 2013. The interdisciplinary scope of research is apparent, with contributions from 54 countries, with China at the forefront. In-depth author and journal analyses exposed key contributors like Zhang L and influential journals like "Lung Cancer". Co-citation networks illuminated crucial references, clusters, and evolving themes over time, underscoring the intricate relationship between inflammation, cancer, and TLS. TLS as a key component of immune response and inflammation, studying its mechanism of impact on cancer will be a potential research direction in the future. This study underscores the pivotal role of inflammation in lung cancer progression, mediated by a delicate balance of immune responses. The emerging prominence of TLS as indicator of adaptive immune responses within the tumor microenvironment (TME) offers intriguing avenues for future research and therapeutic interventions. However, limitations in the current research, such as the need for more longitudinal studies and clinical trials, must be addressed. The insights gained from this bibliometric analysis can inform clinical practices and guide future investigations into novel strategies to improve patient outcomes.