Journal of Translational Autoimmunity最新文献

{"title":"Mechanism of action and promising clinical application of melatonin from a dermatological perspective","authors":"Shan Zhang,&nbsp;Xu Yao","doi":"10.1016/j.jtauto.2023.100192","DOIUrl":"10.1016/j.jtauto.2023.100192","url":null,"abstract":"<div><p>Melatonin is the main neuroendocrine product in the pineal gland. Melatonin can regulate circadian rhythm-related physiological processes. Evidence indicates an important role of melatonin in hair follicles, skin, and gut. There appears to be a close association between melatonin and skin disorders. In this review, we focus on the latest research of the biochemical activities of melatonin (especially in the skin) and its promising clinical applications.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100192"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a0/f3/main.PMC9969269.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10824041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective induction of thymic stromal lymphopoietin expression by novel nitrogen-containing steroid compounds in PAM-212 cells","authors":"Yu Wang ,&nbsp;Ryosuke Segawa ,&nbsp;Yan Weng ,&nbsp;Katsuya Nakai ,&nbsp;Keiichiro Ohashi ,&nbsp;Masahiro Hiratsuka ,&nbsp;Mieko Arisawa ,&nbsp;Noriyasu Hirasawa","doi":"10.1016/j.jtauto.2022.100186","DOIUrl":"10.1016/j.jtauto.2022.100186","url":null,"abstract":"<div><h3>Background</h3><p>Thymic stromal lymphopoietin (TSLP) has been shown to be able to amplify Tregs. Thus, TSLP induction has the potential to induce endogenous Tregs and control autoimmunity. In the previous research, we found that a new compound named 02F04 can induce TSLP production while simultaneously activating the liver X receptor (LXR). Because LXR activation leads to a decrease in Treg, we attempted to find a 02F04-derivative, druggable lead compound with a basic skeleton that induces TSLP production without activating LXR. As the results, we found HA-7 and HA-19 and, in this study, examined the molecular mechanisms in TSLP production.</p></div><div><h3>Methods</h3><p>A murine keratinocyte cell line PAM 212 was stimulated with HA-7 and HA-19, and then the expressions of cytokines were examined via ELISA and real-time fluorescence quantitative PCR.</p></div><div><h3>Results</h3><p>HA-7 and HA-19 induced TSLP production but almost not the expression of TNF-α, IL-13, IL-25, and IL-33 in PAM212 cells. These compounds inhibited LXR activities. The TSLP expression induced by HA-7 and HA-19 was inhibited by the Gq/11 inhibitor YM-254890, ROCK inhibitor Y-27632, and ERK inhibitor U0126. HA-7 and HA-19 also induced the formation of stress fiber and ERK phosphorylation, which were inhibited by YM-254890 and Y-27632.</p></div><div><h3>Conclusions</h3><p>Our findings indicated that HA-7 and HA-19 selectively induced TSLP production in PAM212 via Gq/11, Rho/ROCK and ERK pathways. Our findings also indicated that TSLP expression was differentially regulated from other cytokines, and the selective expression could be induced with low-molecular-weight compounds such as HA-7 and HA-19.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100186"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/03/97/main.PMC9852564.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10579006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scleroderma specific autoantibodies in rheumatoid arthritis and Sjögren's syndrome patients with interstitial lung disease: Prevalence and associations","authors":"Vasiliki Koulouri ,&nbsp;Athanasios-Dimitrios Bakasis ,&nbsp;Nikolaos Marketos ,&nbsp;Kyriaki Tavernaraki ,&nbsp;Mayra Giannelou ,&nbsp;Haralampos M. Moutsopoulos ,&nbsp;Clio P. Mavragani","doi":"10.1016/j.jtauto.2022.100183","DOIUrl":"10.1016/j.jtauto.2022.100183","url":null,"abstract":"<div><p>Systemic sclerosis (SSc) has been classically linked to interstitial lung disease (ILD) development, often in association with specific SSc autoantibodies. In the present report, we aimed to estimate the prevalence of SSc autoantibodies in 60 seropositive RA and 41 primary SS patients complicated or not by ILD. SSc autoantibodies were determined in patients’ sera by a commercial immunoblot assay. RA ILD patients displayed higher frequency of SSc-specific antibodies at strong titers compared to RA-with no lung involvement (25% vs 3.1%, p = 0.01)[OR 95% CI:10.9 (1.2–94.5)], with no differences detected between primary SS groups. These data indicate that many seropositive RA ILD patients probably represent an overlap RA/SSc entity, requiring tailored diagnostic and therapeutic approach.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100183"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/bf/main.PMC9816776.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10508666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Could a simple biomarker as neutrophil-to-lymphocyte ratio reflect complex processes orchestrated by neutrophils?","authors":"María Kourilovitch,&nbsp;Claudio Galarza–Maldonado","doi":"10.1016/j.jtauto.2022.100159","DOIUrl":"10.1016/j.jtauto.2022.100159","url":null,"abstract":"<div><p>The complex pathological mechanisms of autoimmune diseases have now been discovered and described, including interactions between innate and adaptive immunity, the principal cells of which are neutrophils and lymphocytes. Neutrophil-to–lymphocyte ratio (NLR) was proposed as a biomarker for inflammation that reflects the balance between these aspects of the immune system. NLR is widely studied as a prognostic or screening parameter in quantity diseases with important inflammatory components such as malignancies, trauma, sepsis, critical care pathology, etc. Although there are still no consensually accepted normal values for this parameter, there is a proposal to consider an interval of 1–2 as a normal value, an interval of 2–3 as a grey area indicating subclinical inflammation and values above 3 as inflammation.</p><p>On the other hand, several studies have been published indicating that a particular morphological type of neutrophils, low-density neutrophils (LDNs), play a pathological role in autoimmune diseases. Probably, the LDNs detected in patients with different autoimmune diseases, mostly than normal density neutrophils, are involved in the suppression of lymphocytes through different pathways: inducing of lymphopenia through neutrophil depending overproduction of type I interferon (IFN)-α/β and direct suppression by a hydrogen-peroxide-dependent mechanism. Their functional features involvement in IFN production is of particular interest. IFN is one of the critical cytokines in the pathogenesis of many autoimmune diseases, primarily systemic lupus erythematosus (SLE). An interesting and important feature of IFN involvement in the pathogenesis of SLE is not only to be directly related to lymphopenia but also its role in the inhibition of the production of C-reactive protein (CRP) by hepatocytes. The CRP is the primary acute phase reactant, which in SLE often does not correlate with the extent of inflammation. NLR in such a case can be an important biomarker of inflammation. The study of NLR as a biomarker of inflammation also deserves attention in other diseases with established interferon pathways, as well as in hepatopathies, when CRP does not reflect the proper inflammation activity. Also, it may be interesting to study its role as a predictor of relapses in autoimmune diseases.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100159"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/84/55/main.PMC10313502.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9744324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucocorticoids selectively affect the memory T cell response to SARS-Cov2 spike in vaccinated and post-infected patients with systemic lupus erythematosus","authors":"Yves Renaudineau ,&nbsp;Chloé Bost ,&nbsp;Florence Abravanel ,&nbsp;Jacques Izopet ,&nbsp;Antoine Blancher ,&nbsp;Nicolas Congy ,&nbsp;Emmanuel Treiner ,&nbsp;Laurent Sailler","doi":"10.1016/j.jtauto.2023.100200","DOIUrl":"10.1016/j.jtauto.2023.100200","url":null,"abstract":"<div><p>Immune response to vaccines and pathogens remains unclear in patients with systemic lupus erythematosus (SLE). To investigate this, a single-center retrospective study was conducted with 47 SLE patients vaccinated against COVID-19, including 13 who subsequently developed an asymptomatic/mild disease. As compared to controls, post-vaccine response against Spike was reduced in SLE patients when considering both memory T-cells in a whole blood interferon gamma release assay (IGRA-S) and IgG anti-Spike antibody (Ab) responses. The SLE-associated defective IGRA-S response was associated with a serum albumin level below 40 g/L and with the use of glucocorticoids, while a defective IgG anti-Spike Ab response was associated with lower levels of anti-dsDNA and anti-SSA/Ro 52 kDa Abs. IGRA-S and IgG anti-Spike responses were independent from SLE activity and clinical phenotype, low complement, hypergammaglobulinemia, and lymphopenia. As compared to controls, SLE patients showed a rapid decay of anti-Spike T-cell memory and stable IgG anti-Spike Ab responses. In conclusion, both T cell and humoral anti-Spike responses were independently affected in our SLE patients cohort, which supports the exploration of both responses in the follow-up of SLE patients and especially in those receiving glucocorticoids.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100200"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9330591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamine deamidation does not increase the immunogenicity of C-peptide in people with type 1 diabetes","authors":"Abby Foster ,&nbsp;Pushpak Bhattacharjee ,&nbsp;Eleonora Tresoldi ,&nbsp;Miha Pakusch ,&nbsp;Fergus J. Cameron ,&nbsp;Stuart I. Mannering","doi":"10.1016/j.jtauto.2022.100180","DOIUrl":"10.1016/j.jtauto.2022.100180","url":null,"abstract":"<div><p>Type 1 diabetes (T1D) is a T-cell mediated autoimmune disease in which the insulin-producing beta cells are destroyed. While it is clear that full-length C-peptide, derived from proinsulin, is a major antigen in human T1D it is not clear how and why C-peptide becomes a target of the autoimmune CD4⁺ T-cell responses in T1D. Neoepitopes formed by the conversion of glutamine (Q) residues to glutamic acid (E) by deamidation are central to the immune pathogenesis of coeliac disease and have been implicated in autoimmune responses in T1D. Here, we asked if the immunogenicity of full-length C-peptide, which comprises four glutamine residues, was enhanced by deamidation, which we mimicked by substituting glutamic acid for glutamine residue. First, we used a panel of 18 well characterized CD4⁺ T-cell lines specific for epitopes derived from human C-peptide. In all cases, when the substitution fell within the cognate epitope the response was diminished, or in a few cases unchanged. In contrast, when the substitution fell outside the epitope recognized by the TCR responses were unchanged or slightly augmented. Second, we compared CD4⁺ T-cell proliferation responses, against deamidated and unmodified C-peptide, in the peripheral blood of people with or without T1D using the CFSE-based proliferation assay. While, as reported previously, responses were detected to unmodified C-peptide, no deamidated C-peptide was consistently more stimulatory than native C-peptide. Overall responses were weaker to deamidated C-peptide compared to unmodified C-peptide. Hence, we conclude that deamidated C-peptide does not play a role in beta-cell autoimmunity in people with T1D.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100180"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9811213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10858443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 presentation and outcomes in patients with inflammatory rheumatic and musculoskeletal diseases receiving IL6-receptor antagonists prior to SARS-CoV-2 infection","authors":"Cloé Comarmond ,&nbsp;Elodie Drumez ,&nbsp;Julien Labreuche ,&nbsp;Eric Hachulla ,&nbsp;Thierry Thomas ,&nbsp;René-Marc Flipo ,&nbsp;Raphaëlle Seror ,&nbsp;Jérôme Avouac ,&nbsp;Nathalie Balandraud ,&nbsp;Renaud Desbarbieux ,&nbsp;Renaud Felten ,&nbsp;Mélanie Gilson ,&nbsp;Marie-Hélène Guyot ,&nbsp;Ambre Hittinger-Roux ,&nbsp;Thao Pham ,&nbsp;Myriam Renard ,&nbsp;Nicolas Roux ,&nbsp;Vincent Sobanski ,&nbsp;Anne Tournadre ,&nbsp;Christophe Richez ,&nbsp;Patrice Cacoub","doi":"10.1016/j.jtauto.2023.100190","DOIUrl":"10.1016/j.jtauto.2023.100190","url":null,"abstract":"<div><h3>Objective</h3><p>COVID-19 outcome may be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases (RMD) receiving immunosuppressive therapy. We aimed to investigate whether RMD patients on anti-IL6 therapy prior to SARS-CoV-2 infection have less severe disease and better outcomes of COVID-19.</p></div><div><h3>Methods</h3><p>We conducted a retrospective national, multicentre cohort study using data from the French RMD COVID-19 cohort. We compared the severity and outcome of highly suspected or confirmed COVID-19 infection in RMD patients previously treated with tocilizumab or sarilumab (anti-IL6 group) with patients who did not receive anti-IL6 therapy (no anti-IL6 group).</p></div><div><h3>Results</h3><p>Data were collected for 1883 patients with mean age of 55.2 years [SD 16.7] and 1256 (66.7%) female. Two hundred ten (11.1%) developed severe COVID-19 and 115 (6.4%) died. After adjusting for potential confounding factors, severe COVID-19 was less frequent in the anti-IL6 group compared with the no anti-IL6 group (aOR for moderate vs. mild severity, 0.23 [95% CI, 0.10 to 0.54], p ≤ 0.01 and aOR for severe vs. mild, 0.29 [95% CI, 0.10 to 0.81], p ≤ 0.01). No significant differences were found for the evolution of COVID-19 between the anti-IL6 group and the no anti-IL6 group (aOR for recovery with sequelae vs recovery without sequelae, 0.78 [95% CI, 0.41 to 1.48] and aOR for death vs recovery without sequelae, 0.29 [95% CI, 0.07 to 1.30]).</p></div><div><h3>Conclusion</h3><p>RMD patients receiving anti-IL6 therapy prior to SARS-CoV-2 infection have less severe forms of COVID-19. No difference was observed in COVID-19 evolution, i.e., sequelae or death, between the groups.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100190"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d2/70/main.PMC9839461.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10579005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"eNAMPT/TLR4 inflammatory cascade activation is a key contributor to SLE Lung vasculitis and alveolar hemorrhage","authors":"Gantsetseg Tumurkhuu ,&nbsp;Nancy G. Casanova ,&nbsp;Carrie L. Kempf ,&nbsp;Duygu Ercan Laguna ,&nbsp;Sara M. Camp ,&nbsp;Jargalsaikhan Dagvadorj ,&nbsp;Jin H. Song ,&nbsp;Vivian Reyes Hernon ,&nbsp;Cristina Travelli ,&nbsp;Erica N. Montano ,&nbsp;Jeong Min Yu ,&nbsp;Mariko Ishimori ,&nbsp;Daniel J. Wallace ,&nbsp;Saad Sammani ,&nbsp;Caroline Jefferies ,&nbsp;Joe G.N. Garcia","doi":"10.1016/j.jtauto.2022.100181","DOIUrl":"10.1016/j.jtauto.2022.100181","url":null,"abstract":"<div><h3>Rationale</h3><p>Effective therapies to reduce the severity and high mortality of pulmonary vasculitis and diffuse alveolar hemorrhage (DAH) in patients with systemic lupus erythematosus (SLE) is a serious unmet need. We explored whether biologic neutralization of eNAMPT (extracellular nicotinamide phosphoribosyl-transferase), a novel DAMP and Toll-like receptor 4 ligand, represents a viable therapeutic strategy in lupus vasculitis.</p></div><div><h3>Methods</h3><p>Serum was collected from SLE subjects (n = 37) for eNAMPT protein measurements. In the preclinical pristane-induced murine model of lung vasculitis/hemorrhage, C57BL/6 J mice (n = 5–10/group) were treated with PBS, IgG (1 mg/kg), or the eNAMPT-neutralizing ALT-100 mAb (1 mg/kg, IP or subcutaneously (SQ). Lung injury evaluation (Day 10) included histology/immuno-histochemistry, BAL protein/cellularity, tissue biochemistry, RNA sequencing, and plasma biomarker assessment.</p></div><div><h3>Results</h3><p>SLE subjects showed highly significant increases in blood <em>NAMPT</em> mRNA expression and eNAMPT protein levels compared to healthy controls. Preclinical pristane-exposed mice studies showed significantly increased NAMPT lung tissue expression and increased plasma eNAMPT levels accompanied by marked increases in alveolar hemorrhage and lung inflammation (BAL protein, PMNs, activated monocytes). In contrast, ALT-100 mAb-treated mice showed significant attenuation of inflammatory lung injury, alveolar hemorrhage, BAL protein, tissue leukocytes, and plasma inflammatory cytokines (eNAMPT, IL-6, IL-8). Lung RNA sequencing showed pristane-induced activation of inflammatory genes/pathways including NFkB, cytokine/chemokine, IL-1β, and MMP signaling pathways, each rectified in ALT-100 mAb-treated mice.</p></div><div><h3>Conclusions</h3><p>These findings highlight the role of eNAMPT/TLR4-mediated inflammatory signaling in the pathobiology of SLE pulmonary vasculitis and alveolar hemorrhage. Biologic neutralization of this novel DAMP appears to serve as a viable strategy to reduce the severity of SLE lung vasculitis.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100181"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/71/9d/main.PMC9816774.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10508668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exacerbation of psoriasis induced by Nivolumab in a patient with stage IIIc gastric adenocarcinoma: A case report and literature review","authors":"Xiaojie Sun ,&nbsp;Xiaole Mei ,&nbsp;Yi Liu","doi":"10.1016/j.jtauto.2023.100193","DOIUrl":"10.1016/j.jtauto.2023.100193","url":null,"abstract":"<div><p>Nivolumab, the programmed cell death 1 inhibitor, is a kind of immune checkpoint inhibitor commonly used to treat advanced cancers. Unfortunately, such drugs often induce various immune-related adverse events involving different body systems, with psoriasis being one of the skin toxicities. We report the clinical features of an exacerbated psoriasis induced by using nivolumab after three days in a patient with stage IIIc gastric adenocarcinoma. At the same time, we searched 27 case reports published from 2015 to 2021 over the world and systematically summarized the clinical manifestation of a total of 44 cases with psoriasis caused or exacerbated by Nivolumab. Commonly traditional treatment could be useful, and small molecule drugs such as apremilast are effective among some patients. However, more studies are needed to evaluate the efficacy and safety of biologics or small molecule drugs in treating psoriasis induced by nivolumab.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100193"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/31/main.PMC9958049.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10813473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apoptotic biliary epithelial cells and gut dysbiosis in the induction of murine primary biliary cholangitis","authors":"Yu-Wen Wang ,&nbsp;Chia-I Lin ,&nbsp;Hung-Wen Chen ,&nbsp;Jui-Ching Wu ,&nbsp;Ya-Hui Chuang","doi":"10.1016/j.jtauto.2022.100182","DOIUrl":"10.1016/j.jtauto.2022.100182","url":null,"abstract":"<div><p>Primary biliary cholangitis (PBC) is a female-predominant liver autoimmune disease characterized by the specific immune-mediated destruction of the intrahepatic small bile duct. Although apoptosis of biliary epithelial cells (BECs) and alterations in gut microbiota are observed in patients with PBC, it is still unclear whether these events happen in the early stage and cause the breakdown of tolerance in PBC. In this study, we examined the early events in the loss of tolerance in our well-defined 2-OA-OVA-induced murine autoimmune cholangitis (AIC) model. We report herein that apoptosis of BECs was notable in the early stage of murine AIC. An altered gut microbiota, in particular, an increased percentage of gram-positive <em>Firmicutes</em> in AIC mice was also observed. BECs in AIC mice expressed adhesion molecule ICAM-1, cytokines/chemokines TNF-α, CCL2, CXCL9, CXCL10, and toll-like receptor (TLR) 2. Moreover, BECs treated with TLR2 ligand had elevated apoptosis and CXCL10 production. These data collectively suggest a new mechanism of tolerance breakdown in AIC. Altered gut microbiota induces apoptosis of BECs through TLR2 signaling. BECs secrete chemokines to recruit CD8 T cells to damage BECs further.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"6 ","pages":"Article 100182"},"PeriodicalIF":3.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c8/d0/main.PMC9811212.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10858444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}