Primary Sjögren’s syndrome (pSS) is characterized by a panel of autoantibodies, while it is not clear whether B cells and autoantibodies play an essential role in pathogenesis of the disease. Here, we report a novel mouse model for pSS which is induced by immunization with the Ro60_316-335 peptide containing a predominant T cell epitope. After immunization, mice developed several symptoms mimicking pSS, including a decreased secretion of tears, lymphocytic infiltration into the lacrimal glands, autoantibodies, and increased levels of inflammatory cytokines. Disease susceptibility to this novel mouse model varies among strains, where C3H/HeJ (H2-k) and C3H/HeN (H2-k) are susceptible while DBA/1 (H2-q) and C57BL/6 (H2-b) are resistant. Depletion of B cells using anti-CD20 monoclonal antibodies prevented C3H/HeN mice from development of the pSS-like disease. In addition, HLA-DRB1*0803, a pSS risk allele, was predicted to bind to the hRo60_308-328 which contains a predominant T cell epitope of human Ro60. Therefore, this study provides a novel mouse model for pSS and reveals an indispensable role of B cells in this model. Moreover, it suggests that T cell epitope within Ro60 antigen is potentially pathogenic for pSS.

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gp130 cytokines are differentially involved in regulating the T helper (H) 17-driven pathogenesis of experimental autoimmune encephalomyelitis (EAE), the animal model of human multiple sclerosis. Interleukin (IL)-6 directly promotes the development of TH17 cells through the gp130/IL-6R complex. By contrast, IL-27 has been shown to suppress a TH17 immune response by gp130/IL-27R-alpha (α) receptor ligation. The IL-27-dependent regulation of a TH17 development could be mediated on the level of CD4 T cells. However, because IL-27 also suppresses the secretion of the TH17-driving cytokines IL-6 and IL-12/23p40 in accessory cells, TH17 immune responses may also be controlled by IL-27 on the level of macrophages and/or neutrophils. To analyze these opposing effects of gp130 engagement on the pathogenesis of EAE, we immunized CD4+ T cell-specific gp130-deficient (CD4creposgp130loxP/loxP) and macrophage/neutrophil-specific gp130-deficient (LysMcreposgp130loxP/loxP) mice with the myelin-oligodendrocyte-glycoprotein peptide MOG35–55. Whereas inflammatory immune responses, TH17 differentiation, and pathology in CD4creposgp130loxP/loxP mice were mitigated, disease progression was eventually enhanced in LysMcreposgp130loxP/loxP mice. Exacerbated disease in MOG35–55-immunized LysMcreposgp130loxP/loxP mice was associated with an elevated development of TH17 cells and increased infiltration of the central nervous system with leukocytes indicating a suppressive role of macrophage/neutrophil-gp130. To further prove IL-6 to be responsible for the control of inflammation during EAE through gp130 on macrophages/neutrophils, we immunized LysMcreposIL-6RloxP/loxP mice. In contrast to LysMcreposgp130loxP/loxP mice, neuropathology in MOG35–55-immunized macrophage/neutrophil-specific IL-6R-deficient mice was not enhanced indicating that the alleviation of EAE through macrophage/neutrophil-gp130 is mediated independently of IL-6. Together, this different pathology in macrophage/neutrophil- and CD4 T cell-specific gp130-deficient mice suggests that gp130 cytokines modulate TH17 inflammation differentially by targeting distinct cell types.

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Aim: Primary Sj€ ogren's syndrome (pSS) is an autoimmune disease affecting exocrine glands. Both autoreactive T cells and B cells are involved in the development of pSS, but their exact contribution to the pathogenesis is not clear. Here, we aimed to investigate the association of B-cell activating factor (BAFF) and interleukin (IL)-17A with subphenotypes of pSS.Methods: Peripheral blood samples were collected from 31 pSS patients and 28 healthy controls. The serum levels of BAFF and IL-17A were quantified by sandwich ELISA. Results:The increased circulating BAFF levels are associated with higher immunoglobulin G (IgG) levels (P = 0.0167) and anti-Ro/SS antigen A autoantibody (P = 0.032), while the elevated circulating levels of IL-17A are associated with lower C3 levels (P = 0.0213) and higher focus score of salivary gland tissue (P = 0.002). Conclusion:Our results show that BAFF and IL-17A are associated with different subphenotypes of pSS, suggesting both humoral and cellular immune response are involved in the pathogenesis of pSS.

CD11b, the α-chain of β 2 integrin Mac-1, is involved in many activation processes of phagocytes. Depending on the respective autoimmune disorder, CD11b has been shown to exert pro-inflammatory functions or be dispensable in their pathogenesis. Here, we investigated the role of CD11b in the pathogenesis of experimental epidermolysis bullosa acquisita (EBA), an autoimmune skin blistering disease mediated by autoantibodies to type VII collagen. Unexpectedly, in an antibody transfer-induced model of EBA, CD11b-deficient mice developed more severe disease symptoms than wild-type mice in the late phase of the disease. Furthermore, as compared to wild-type controls, CD11b-deficient mice expressed increased levels of circulating IFN-γ and IL-4. Taken together, for the first time, our results suggest an anti-inflammatory role for CD11b in experimental autoimmune diseases.

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Ectopic expression of MHC II molecules on glandular cells is a feature of primary Sjögren's syndrome (pSS). However, the cause of this ectopic expression and its potential role in the pathogenesis of the disease remains elusive. Here, we report that ectopic expression of MHC II molecules on glandular cells represents an early presymptomatic event in a mouse model of pSS induced by immunization of Ro60_316-335 peptide emulsified in TiterMax® as an adjuvant. Ectopic expression of MHC II was induced by TiterMax® but not by complete freund's adjuvant (CFA). Furthermore, immunization with Ro60_316-335 peptide emulsified in TiterMax®, but not in CFA, induced a pSS-like disease in mice. Our results suggests that ectopic expression of MHC II molecules on glandular cells represents a presymptomatic feature of pSS and that such ectopic expression can be induced by exogenous factors. In addition, this study also provides a novel mechanism how adjuvants can amplify immune responses.