Amelioration of autoimmune arthritis by adoptive transfer of Foxp3-expressing regulatory B cells is associated with the Treg/Th17 cell balance

作者:Park Mi Kyung; Jung Young Ok; Lee Seon Yeong; Lee Seung Hoon; Heo Yu Jung; Kim Eun Kyung; Oh Hye Jwa; Moon Young Mee; Son Hye Jin; Park Min Jung; Park Sung Hwan; Kim Ho Youn; La Cho Mi*; Min Jun Ki*
来源:Journal of Translational Medicine, 2016, 14(1): 191.
DOI:10.1186/s12967-016-0940-7

摘要

Background: Foxp3 is a key regulator of the development and function of regulatory T cells (Tregs), and its expression is thought to be T cell-restricted. We found that B cells in mice can express Foxp3 and B cells expressing Foxp3 may play a role in preventing the development of collagen-induced arthritis (CIA) in DBA/1J mice. Methods: Foxp3 expression was modulated in CD19(+) B cells by transfection with shRNA or using an over-expression construct. In addition, Foxp3-transfected B cells were adoptively transferred to CIA mice. We found that LPS or anti-IgM stimulation induced Foxp3 expression in B cells. Foxp3-expressing B cells were found in the spleens of mice. Results: Over-expression of Foxp3 conferred a contact-dependent suppressive ability on proliferation of responder T cells. Down-regulation of Foxp3 by shRNA caused a profound induction in proliferation of responder T cells. Adoptive transfer of Foxp3(+)CD19(+) B cells attenuated the clinical symptoms of CIA significantly with concomitant suppression of IL-17 production and enhancement of Foxp3 expression in CD4(+) T cells from splenocytes. Conclusion: Our data indicate that Foxp3 expression is not restricted to T cells. The expression of Foxp3 in B cells is critical for the immunoregulation of T cells and limits autoimmunity in a mouse model.