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Acute myeloid leukemia (AML) is a blood cancer that is caused by a disorder of the process that normally generates neutrophils. Function and dysfunction of neutrophils are key to physiologic defense against pathogens as well as pathologies including autoimmunity and cancer. A major mechanism through which neutrophils contribute to health and disease is oxidative burst, which involves rapid release of reactive oxygen species (ROS) generated by a chemical reaction network catalyzed by enzymes including NADPH oxidase and myeloperoxidase (MPO). Due to the involvement of neutrophil-derived reactive oxygen species in many diseases and importance of NADPH oxidase and MPO-mediated reactions in progression and treatment of myeloid leukemia, monitoring this process and modulating it by pharmacological interventions is of great interest. In this work, we have evaluated the potential of a label-free method using ultra-weak photon emission (UPE) to monitor ROS production in neutrophil-like HL60 myeloid leukemia cells. Suppression of ROS was achieved by several drug candidates that target different parts of the reaction pathway. Our results show that UPE can report on ROS production as well as suppression by pharmacological inhibitors. We find that UPE is primarily generated by MPO catalyzed reaction and thus will be affected when an upstream reaction is pharmacologically modulated.

// Hui Wang 1 , Wenrong Xu 2 , Qixiang Shao 1 and Qing Ding 1 1 Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P.R. China 2 Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P.R. China Correspondence to: Qixiang Shao, email: shao_qx@ujs.edu.cn Qing Ding, email: qing_ding69@163.com Keywords: microRNA-21, interleukin-10, regulatory B cells, experimental autoimmune encephalomyelitis Received: June 29, 2017 Accepted: September 18, 2017 Published: October 06, 2017 ABSTRACT IL-10-producing regulatory B (IL-10 + Breg) cells promote tolerance in autoimmune diseases and transplantation. However, it remains unclear whether microRNAs are involved in the development of IL-10 + Breg cells. Here, we found that microRNA-21 (miR-21) acts as an upstream regulator of IL-10 by targeting the 3' untranslated region of IL-10 mRNA. We also demonstrated that IL-10 + Breg cells exhibit lower miR-21 expression than non-Breg cells and that miR-21 acts as a potent negative regulator of the differentiation of IL-10 + Breg cells. Accordingly, specific inhibition of miR-21 using antisense oligonucleotides markedly promoted B cell IL-10 expression. Thus, IL-10 is a direct target of miR-21. Moreover, silencing of miR-21 significantly alleviated the severity of experimental autoimmune encephalomyelitis (EAE), and this change was associated with an increase in the number of IL-10 + Breg cells. Finally, we demonstrated that miR-21-silenced B cells exert their suppressive activity through effector T cells in an IL-10-dependent manner. Thus, we characterized a B cell-intrinsic microRNA pathway that inhibits the differentiation of IL-10 + Breg cells and promotes autoimmunity. miR-21 silencing therefore represents a new therapeutic strategy for the treatment of autoimmune diseases.

// Xiaolu Huang 1, * , Yiwen Zhou 1, * , Wenhui Liu 1 , Haizhou Li 1 , Xiao Liang 1 , Rui Jin 1 , Hengyu Du 1 , Jizhou He 1 , Bangda Chai 1 , Ran Duan 1 and Qingfeng Li 1 1 Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R.China * These authors contributed equally to this work and should be considered as co-author Correspondence to: Qingfeng Li, email: dr.liqingfeng@shsmu.edu.cn Keywords: silicone implant, autoimmunity, microarray, WGCNA, hub genes Received: July 04, 2017 Accepted: September 21, 2017 Published: October 06, 2017 ABSTRACT Silicone implants are used widely in the field of plastic surgery and are used in a large population. However, their safety profile, especially the silicone-induced immune response, has been a major concern for plastic surgeons for decades. It has been hypothesized that there is a cause and effect relation between silicone and immunity, but this is controversial. The objective of the present study was to determine the hub genes and key pathways related to silicone implant–induced immune responses in a rat model. In addition to cluster and enrichment analyses, we used weighted gene co-expression network analysis (WGCNA) to examine the gene expression profiles in a systematic context. A total five genes ( Fes , Aif1 , Gata3 , Tlr6 , Tlr2 ) were identified as hub genes that are most likely related to the silicone-induced immune response, four of which ( Aif1 , Gata3 , Tlr6 , Tlr2 ) have been associated with autoimmunity as target genes or disease markers. The Toll-like receptor signaling pathway ( p < 0.01, fold enrichment: 7.01) and systemic lupus erythematosus signaling pathway ( p < 0.05, fold enrichment: 5.01), which are considered strongly associated with autoimmunity, were significantly enriched in the silicone-implanted skin samples. The results indicate that silicone implants might trigger the localized immune response, as various immune reaction genes were detected after silicone implantation. The identified five hub genes will hopefully serve as novel therapeutic targets for silicone-related complications and the associated autoimmune diseases.

// Yeshu Wang 1, * , Qingfeng Xie 2, * , Chun-Ling Liang 3, * , Qiaohuang Zeng 1 and Zhenhua Dai 3 1 Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China 2 Center for Regenerative and Translational Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, P.R. China 3 Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, P.R. China * These authors have contributed equally to this work Correspondence to: Zhenhua Dai, email: zdai2009@outlook.com Keywords: autoimmunity, type 1 diabetes, regulatory T cells, Chinese medicine Abbreviations: CsA, cyclosporine; GAG, ginseng and astragalus granule; T1DM, type 1 diabetes mellitus; Treg, regulatory T cell Received: March 21, 2017 Accepted: April 27, 2017 Published: June 27, 2017 ABSTRACT Type 1 diabetes mellitus (T1DM) is an autoimmune disease mainly mediated by effector T cells that are activated by autoantigen, thereby resulting in the destruction of pancreatic islets and deficiency of insulin. Cyclosporine is widely used as an immunosuppressant that suppresses autoimmunity in clinic. However, continuous treatments with conventional immunosuppressive drugs may cause severe side effects. Therefore it is important to seek alternative medicine. Chinese medicine Ginseng and Astragalus granule (GAG) was used to successfully treat type 2 diabetes mellitus in clinic in China. Here we found that GAG ameliorated T1DM in autoimmune NOD mice by increasing the level of insulin and reducing the level of blood glucose. Treatments with both GAG and CsA further decreased the blood glucose level. Moreover, GAG increased both CD4+FoxP3+ and CD8+CD122+PD-1+ Treg numbers in both spleens and lymph nodes of NOD mice. In particular, GAG could reverse a decline in CD4+FoxP3+ Tregs resulted from CsA treatments. The percentage of effector/memory CD8+ T cells (CD44 high CD62L low ) was significantly reduced by GAG, especially in the presence of low-doses of CsA. Histopathology also showed that GAG attenuated cellular infiltration and lowered CD3+ T cell numbers around and in islets. Thus, we demonstrated that GAG ameliorated autoimmune T1DM by upregulating both CD4+FoxP3+ and CD8+CD122+PD-1+ Tregs while GAG synergized with CsA to further suppress autoimmunity and T1DM by reversing the decline in CD4+FoxP3+ Tregs resulted from CsA treatments. This study may have important clinical implications for the treatment of T1DM using traditional Chinese medicine.

// Jeong-Eun Lee 1,2,* , Jung-Man Lee 3,* , Young-Jun Park 1 , Byung-Seok Kim 1,2 , Young-Tae Jeon 4,5 and Yeonseok Chung 1,2 1 Laboratory of Immune Regulation, Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, Republic of Korea 2 BK21 plus program, College of Pharmacy, Seoul National University, Seoul, Republic of Korea 3 Department of Anesthesiology and Pain Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea 4 Department of Anesthesiology and Pain Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea 5 Department of Anesthesiology and Pain Medicine, College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea * These authors have equally contributed to this work Correspondence to: Yeonseok Chung, email: // Young-Tae Jeon, email: // Keywords : ketamine, Th17 cell, STAT3, IL-21, autoimmunity, Immunology and Microbiology Section, Immune response, Immunity Received : April 04, 2017 Accepted : May 23, 2017 Published : May 31, 2017 Abstract Ketamine is widely used in animals and humans as a systemic anesthetic. Although several immune-modulatory functions of ketamine have been reported, the effects of ketamine on the differentiation of Th17 cell are unknown. We found that ketamine significantly diminished the frequency of IL-17-producers among CD4 + T cells stimulated under Th17-skewing conditions. Mechanistic studies showed that ketamine had little effect on the production of Th17-inducing cytokines by dendritic cells and the proliferation of T cells in response to anti-CD3; however it significantly hampered IL-21 expression as well as STAT3 phosphorylation in T cells upon IL-6 stimulation. Moreover, MOG-reactive CD4 + T cells expanded in the presence of ketamine produced reduced amounts of Th17 cytokines, leading to diminished EAE severity when transferred into TCRβ-deficient mice in comparison to those treated with vehicle. These findings demonstrate that ketamine suppresses autoimmune Th17 cell responses by inhibiting the differentiation as well as the reactivation of Th17 cells.

Interferon regulatory factor 5 (IRF5) plays a critical role in the induction of type I interferon, proinflammatory cytokines and chemokines, and participates in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). However, the relationship between IRF5 and childhood-onset SLE remains elusive. In the present study, we demonstrated that levels of mRNA expression of IRF5, IFN-α, and Sp1 were significantly increased in childhood-onset SLE, as seen on quantitative real-time PCR, and the expression of Sp1 and IFN-α was positively correlated with IRF5. In addition to being used as antitumor drugs, a number of histone deacetylase inhibitors (HDACi) display potent anti-inflammatory properties; however, their effects on IRF5 expression remain unclear. In this study, we identified that HDACi trichostatin A (TSA) and histone acetyltransferase (HAT)-p300 downregulated IRF5 promoter activity, mRNA expression, and protein level, whereas the HAT-p300/CBP-associated factor had no effect. Moreover, TSA inhibited the production of TNF-α and IL-6 in differentiated THP-1cells. Furthermore, chromatin immunoprecipitation assays revealed that TSA inhibited DNA binding of Sp1, RNA polymerase II, HDAC3, and p300 to the core promoter region of IRF5. Our results suggest that HDACi may have therapeutic potential in patients with autoimmune diseases such as SLE through repression of IRF5 expression.

// Lei Tu 1,* , Jie Chen 2,* , Dandan Xu 2 , Zhongming Xie 2 , Bing Yu 3 , Ying Tao 3 , Guixiu Shi 3 and Lihua Duan 3 1 Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China 2 College of Medicine, Xiamen University, Fujian, China 3 Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China * These authors have contributed equally to this work Correspondence to: Lihua Duan, email: // Guixiu Shi, email: // Keywords : IL-33, inflammatory bowel disease, macrophage, M2, Arginase-1, Immunology and Microbiology Section, Immune response, Immunity Received : January 17, 2017 Accepted : February 28, 2017 Published : March 07, 2017 Abstract Accumulated data have shown that alternatively activated macrophage exerts a modulatory role in many diseases, including colitis. Interleukin-33 (IL-33), a critical modulator in adaptive and innate immune, has been implicated in autoimmunity and inflammation. Previously, we have reported that IL-33 functions as a protective modulator in TNBS-induced colitis, which is closely related to a Th1-to-Th2/Treg switch. Here, we present novel evidence suggesting that IL-33 primes macrophage into alternatively activated macrophages (AAM) in TNBS-induced colitis. The strong polarized effect of IL-33 was tightly associated with the markedly increased induction of Th2-type cytokines. To confirm the beneficial effects of AAM induced by IL-33, peritoneal AAMs isolated from IL-33-treated mice were transferred to recipient mice with TNBS colitis. The adoptive transfer resulted in prominent inhibition of disease activity and inflammatory cytokines in the TNBS-treated mice. In conclusion, our data provide clear evidence that IL-33 plays a protective role in TNBS-induced colitis, which is closely related to AAM polarization.

// Donghee Kim 1 , Jae Young Kim 2 and Hee-Sook Jun 1,3,4 1 Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea 2 Department of Life Science, Gachon University, Seongnam, Gyeonggi-Do, Republic of Korea 3 College of Pharmacy and Gachon Institute Pharmaceutical Science, Gachon University, Incheon, Republic of Korea 4 Gil Medical Research Institute, Gil Hospital, Incheon, Republic of Korea Correspondence to: Hee-Sook Jun, email: // Keywords : Sjogren’s syndrome, Smad4, TGF-beta, NOD mice, IL-17, Immunology and Microbiology Section, Immune response, Immunity Received : May 05, 2016 Accepted : November 07, 2016 Published : November 17, 2016 Abstract We investigated the role of Smad4, a signaling molecule of the TGF-beta pathway, in T cells on the pathology of Sjogren’s syndrome (SS) in nonobese diabetic (NOD) mice, an animal model of SS. T cell-specific Smad4-deleted (Smad4 fl/fl,CD4-Cre ; Smad4 tKO) NOD mice had accelerated development of SS compared with wild-type (Smad4 +/+,CD4-Cre ; WT) NOD mice, including increased lymphocyte infiltration into exocrine glands, decreased tear and saliva production, and increased levels of autoantibodies at 12 weeks of age. Activated/memory T cells and cytokine (IFN-γ, IL-17)-producing T cells were increased in Smad4 tKO NOD mice, however the proportion and function of regulatory T (Treg) cells were not different between Smad4 tKO and WT NOD mice. Effector T (Teff) cells from Smad4 tKO NOD mice were less sensitive than WT Teff cells to suppression by Treg cells. Th17 differentiation capability of Teff cells was similar between Smad4 tKO and WT NOD mice, but IL-17 expression was increased under inducible Treg skewing conditions in T cells from Smad4 tKO NOD mice. Our results demonstrate that disruption of the Smad4 pathway in T cells of NOD mice increases Teff cell activation resulting in upregulation of Th17 cells, indicating that Smad4 in T cells has a protective role in the development of SS in NOD mice.

// Huai-Chia Chuang 1,* , Yi-Ming Chen 2,3,4,* , Wei-Ting Hung 2 , Ju-Pi Li 1 , Der-Yuan Chen 2,3,4 , Joung-Liang Lan 5,6 and Tse-Hua Tan 1,7,8 1 Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan 2 Division of Allergy, Immunology, and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan 3 Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan 4 Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan 5 School of Medicine, China Medical University Hospital, Taichung, Taiwan 6 Division of Rheumatology and Immunology, China Medical University Hospital, Taichung, Taiwan 7 Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan 8 Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA * These authors have contributed equally to this work Correspondence to: Tse-Hua Tan, email: // Joung-Liang Lan, email: // Der-Yuan Chen, email: // Keywords : JKAP, DUSP22, SLE, nephritis, T cells, Immunology and Microbiology Section, Immune response, Immunity Received : March 04, 2016 Accepted : August 13, 2016 Published : August 19, 2016 Abstract Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is characterized by systemic inflammation and multiple organ failures. Dysregulation of T cells plays a critical role in SLE pathogenesis. Our previous study indicates that JKAP (also named DUSP22) inhibits T-cell activation and that JKAP knockout mice develop spontaneous autoimmunity; therefore, we investigated whether JKAP downregulation is involved in SLE patients. JKAP protein levels in purified T cells were examined by immunoblotting using blood samples from 43 SLE patients and 32 healthy controls. SLE patients showed significantly decreased JKAP protein levels in peripheral blood T cells compared to healthy controls. JKAP protein levels in peripheral blood T cells were inversely correlated with SLE disease activity index (SLEDAI) and anti-dsDNA antibody levels. JKAP downregulation in T cells was highly correlated with daily urinary protein amounts and with poor renal outcome in lupus nephritis patients. Notably, the diagnostic power of JKAP downregulation in T cells for active lupus nephritis was higher than those of serum anti-dsDNA antibody, C3, and C4 levels. Moreover, T-cell-specific transgenic mice expressing a dominant-negative JKAP mutant developed spontaneous autoimmune nephritis. Furthermore, JKAP-deficient T cells overproduced complement components, soluble ICAM-1, and soluble VCAM-1 in the kidney; these cytokines have been reported to be involved in lupus nephritis. Taken together, JKAP downregulation in T cells is a novel diagnostic and prognostic biomarker for SLE nephritis.

// Xiaojing Jin 1,3,* , Shujun Wang 2,* , Xuemin Zhao 1 , Qian Jin 1 , Chenling Fan 1 , Jing Li 1 , Zhongyan Shan 1 and Weiping Teng 1 1 Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Affiliated Hospital, China Medical University, Liaoning Provincial Key Laboratory of Endocrine Diseases, Shenyang, P. R. China 2 Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P. R. China 3 Present address: Department of Emergency, The First Affiliated Hospital of Hebei Medical University, Shijiazhuang, P.R. China * These authors have contributed equally to this work Correspondence to: Jing Li, email: // Keywords : autoimmunity; thyroiditis; coumestrol; phytoestrogen; T helper cell; Immunology and Microbiology Section; Immune response; Immunity Received : January 29, 2016 Accepted : June 15, 2016 Published : June 30, 2016 Abstract Coumestrol is a common phytoestrogen found in plants and Chinese medicinal herbs. Its influences on experimental autoimmune thyroiditis (EAT) were investigated in this study. Female adult CBA/J mice were fed with drinking water containing 1% Tween80 only (Control group), 0.8 mg/l (L group) and 8 mg/l coumestrol (H group) from 6 to 15 weeks of age, respectively. Their serum coumestrol concentrations were determined by high performance liquid chromatography, which were undetectable, 43.70 ± 21.74 ng/ml and 135.07 ± 70.40 ng/ml, respectively. In addition, the mice (n = 14–16/group) were immunized twice with thyroglobulin (Tg) and Freund’s adjuvant to induce EAT during the meantime. Although no overt changes in the extent of intrathyroidal mononuclear cell infiltration were shown in the two coumestrol-treated groups as compared with the controls, serum anti-Tg IgG2a, IgG3 and IgG1 titers, ratio of IgG2a to IgG1 and the percentage of T helper (Th)1 cells in the splenocytes were significantly reduced in the L group. Another consistent change was the significantly decreased expression of splenic IFN-γ mRNA after low dose of coumestrol exposure. Uterine weight was also markedly reduced in the mice of L group. These findings suggest that coumestrol treatment may have some beneficial actions against thyroid-specific autoantibody production in the development of autoimmune thyroiditis through suppression of Th1 response due to its anti-estrogenic activity.

// Eva Bauer 1 , Michaela Schlederer 1,2 , Ruth Scheicher 3 , Jaqueline Horvath 1,4 , Petra Aigner 1 , Ana-Iris Schiefer 2 , Renate Kain 2 , Heinz Regele 2 , Gregor Hoermann 5 , Gunter Steiner 6,7 , Lukas Kenner 1,2,8 , Veronika Sexl 3 , Andreas Villunger 9,10 , Richard Moriggl 1,5,11 and Dagmar Stoiber 1,4 1 Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria 2 Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria 3 Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria 4 Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria 5 Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria 6 Cluster Arthritis and Rehabilitation, Ludwig Boltzmann Society, Vienna, Austria 7 Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria 8 Unit of Pathology of Laboratory Animals, University of Veterinary Medicine, Vienna, Austria 9 Division of Developmental Immunology, Biocenter, Medical University Innsbruck, Innsbruck, Austria 10 Tyrolean Cancer Research Institute, Innsbruck, Austria 11 Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Vienna, Austria Correspondence to: Dagmar Stoiber, email: // Keywords : ETV6/RUNX1, BCL2, glomerulonephritis, lymphoma, autoimmunity, Immunology and Microbiology Section, Immune response, Immunity Received : September 11, 2015 Accepted : January 31, 2016 Published : February 23, 2016 Abstract The t(12;21) translocation generating the ETV6/RUNX1 fusion gene represents the most frequent chromosomal rearrangement in childhood leukemia. Presence of ETV6/RUNX1 alone is usually not sufficient for leukemia onset, and additional genetic alterations have to occur in ETV6/RUNX1-positive cells to cause transformation. We have previously generated an ETV6/RUNX1 transgenic mouse model where the expression of the fusion gene is restricted to CD19-positive B cells. Since BCL2 family members have been proposed to play a role in leukemogenesis, we investigated combined effects of ETV6/RUNX1 with exogenous expression of the antiapoptotic protein BCL2 by crossing ETV6/RUNX1 transgenic animals with Vav-BCL2 transgenic mice. Strikingly, co-expression of ETV6/RUNX1 and BCL2 resulted in significantly shorter disease latency in mice, indicating oncogene cooperativity. This was associated with faster development of follicular B cell lymphoma and exacerbated immune complex glomerulonephritis. ETV6/RUNX1-BCL2 double transgenic animals displayed increased B cell numbers and immunoglobulin titers compared to Vav-BCL2 transgenic mice. This led to pronounced deposition of immune complexes in glomeruli followed by accelerated development of immune complex glomerulonephritis. Thus, our study reveals a previously unrecognized synergism between ETV6/RUNX1 and BCL2 impacting on malignant disease and autoimmunity.

Mutations in STAT3 have recently been shown to cause autoimmune diseases through increased lymphoproliferation. We describe a novel Pro471Arg STAT3 mutation in a patient with multiple autoimmune diseases, causing hyperactivation of the Th17 pathway. We show that IL-17 production by primary T cells was enhanced and could not be further increased by IL-6, while IL-10 reduced Th17 cell numbers. Moreover, specific inhibition of STAT3 activation resulted in diminished IL-17 production. We show that the Pro471Arg STAT3 mutation yields both increased levels of IgA and IgG, probably due to high IL-21 levels. When remission was reached through medical intervention, IL-17 levels normalized and the clinical symptoms improved, supporting the idea that STAT3 gain-of-function mutations can cause hyperactivation of the Th17 pathway and thereby contribute to autoimmunity.

International audience; Abnormal overexpression of CXCL13 is observed in many inflamed tissues and in particular in autoimmune diseases. Myasthenia gravis (MG) is a neuromuscular disease mainly mediated by anti-acetylcholine receptor autoantibodies. Thymic hyperplasia characterized by ectopic germinal centers (GCs) is a common feature in MG and is correlated with high levels of anti-AChR antibodies. We previously showed that the B-cell chemoattractant, CXCL13 is overexpressed by thymic epithelial cells in MG patients. We hypothesized that abnormal CXCL13 expression by the thymic epithelium triggered B-cell recruitment in MG. We therefore created a novel transgenic (Tg) mouse with a keratin 5 driven CXCL13 expression. The thymus of Tg mice overexpressed CXCL13 but did not trigger B-cell recruitment. However, in inflammatory conditions, induced by Poly(I:C), B cells strongly migrated to the thymus. Tg mice were also more susceptible to experimental autoimmune MG (EAMG) with stronger clinical signs, higher titers of anti-AChR antibodies, increased thymic B cells, and the development of germinal center-like structures. Consequently, this mouse model finally mimics the thymic pathology observed in human MG. Our data also demonstrated that inflammation is mandatory to reveal CXCL13 ability to recruit B cells and to induce tertiary lymphoid organ development.