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

• Published in: Journal of translational medicine 2016-06, Vol.14 (1), p.191-191, Article 191
• Main Authors: 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, Cho, Mi-La, Min, Jun-Ki
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Arthritis; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; B-Lymphocytes, Regulatory - immunology; Care and treatment; Cell Communication; Cell Line, Tumor; Cell Proliferation; Collagen; Dosage and administration; Forkhead Transcription Factors - metabolism; Gene expression; Immunoglobulin M - metabolism; Immunosuppression Therapy; Lipopolysaccharides; Male; Mice, Inbred DBA; Spleen - pathology; T cells; T-Lymphocytes, Regulatory - immunology; Th17 Cells - immunology; Transfection
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-016-0940-7

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. 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. 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. 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.