CD22 and CD72 contribute to the development of scleroderma in a murine model
JOURNAL OF DERMATOLOGICAL SCIENCE
Authors: Zhao, Chunyan; Matsushita, Takashi; Vinh Thi Ha Nguyen; Tennichi, Momoko; Fujimoto, Manabu; Takehara, Kazuhiko; Hamaguchi, Yasuhito
Abstract
Background: Systemic sclerosis (SSc) is a systemic autoimmune disease that is characterized by excessive fibrosis. CD22 and CD72 are B cell-specific cell surface molecules that negatively regulate B cell function. Objective: The aim of the present study was to investigate the roles of CD22 and CD72 in a murine scleroderma model. Methods: The experimental fibrosis model was generated by subcutaneous injection of bleomycin or hypochlorous acid (HOCL) into wild-type (WT), CD22-deficient (CD22(-/-)), CD72-deficient (CD72(-/-)) and CD22 and CD72 double-deficient (CD22(-/-)/CD72(-/-)) mice. We histologically assessed skin fibrosis and inflammatory cell infiltration. Cytokine and chemokine expression levels were measured by real-time polymerase chain reaction. Results: The severity of fibrosis in the skin and lung was significantly less in CD22(-/-), CD72(-/-), and CD22(-/-)/CD72(-/-)mice than in WT mice in the bleomycin-induced model. In the skin of bleomycintreated mice, the numbers of CD3(+) T cells, CD8(+) T cells, and F4/80+ macrophages were significantly lower in CD22(-/-), CD72(-/-), and CD22-/-/CD72(-/-) mice than in WT mice. The expression levels of mRNAs for IL-6, TNF-alpha , TGF-beta, CTGF, IL-1 beta, IL-13, CXCL2, and ICAM-1 were significantly lower in CD22(-/-), CD72(-/-), and CD22-/-/CD72-/-mice than in WT mice. In the HOCL-induced model, both skin and lung fibrosis were ameliorated in CD22(-/-), CD72(-/-) and CD22(-/-)/CD72 mice compared to WT mice. Conclusion: These results indicate that CD22 and CD72 likely play crucial roles in skin and lung fibrosis. Moreover, the inhibition of CD22 and CD72 function has potential as a therapeutic approach to SSc. (C) 2019 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
Evidence for the existence of regulatory and effector B cell populations in Peyer's patches of sheep
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
Authors: Jimbo, S.; Griebel, P. J.; Townsend, H.; Babiuk, L. A.; Mutwiri, G.
Abstract
IL-10 secreting CD21(+) B cells exist in sheep Peyer's patches (PP). It's not known however, whether all PP B cells are regulatory or whether an effector population also exists in this tissue. To further characterize the subpopulations of B cells in PP's, highly purified B cells were negatively sorted from jejunal PP and fractionated according to co-expression of CD72(+)CD21(+) or CD72(+)CD21(-) molecules and then stimulated with the TLR9-agonist, CpG ODN. IL-10, IL-12, IFN-gamma, and IgM production were then assayed. We observed that only highly purified CD72(+)CD21(+) B cells spontaneously secreted high levels of IL-10, but they did not produce any IL-12, IFN-gamma or IgM suggesting that this cell population contains regulatory B cells. In contrast, CD72(+)CD21(-) B cells did not secrete IL-10, but secreted IL-12, IFN-gamma, and IgM, suggesting they include effector cells. In addition, B cells expressing surface IgA, IgM and IgG1 all secreted similar levels of IL-10. We further confirmed that only B cells produce IL-10, while other cells in the PP including DCs and T cells do not. Our investigations may provide evidence for the existence of two sub-populations in sheep PP; IL-10 secreting regulatory (CD72(+)CD21(+)) cells, and IL-12/IFN-gamma/IgM-secreting effector (CD72+CD21-) cells. (C) 2016 Published by Elsevier B.V.