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

Journal of Translational Medicine

Research

Jun Ki Min¹  Ho Youn Kim²  Sung Hwan Park²  Young Ok Jung³  Seon-Yeong Lee⁴  Eun Kyung Kim⁴  Hye-Jin Son⁴  Mi La Cho⁴  Yu Jung Heo⁴  Seung Hoon Lee⁴  Mi Kyung Park⁴  Hye Jwa Oh⁴  Young Mee Moon⁴  Min Jung Park⁴ 

[1] Bucheon St. Mary’s Hospital, Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 327 Sosa-ro, Wonmi-gu, 420-717, Bucheon, Gyeonggi-do, South Korea;Division of Rheumatology, Department of Internal Medicine, College of Medicine, Holy Family Hospital, Rheumatism Research Center (RhRC), Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea;Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea;Division of Rheumatology, Department of Internal Medicine, Hallym University Kang-Nam Sacred Heart Hospital, Seoul, South Korea;The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, 137-040, Seoul, South Korea;

关键词: Foxp3;    Regulatory B cell;    Th17;    Arthritis;   

DOI  :  10.1186/s12967-016-0940-7

 received in 2015-07-14, accepted in 2016-06-11,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundFoxp3 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.MethodsFoxp3 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.ResultsOver-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.ConclusionOur 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.

【 授权许可】

CC BY   
© The Author(s) 2016