The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Interleukin-35 induces regulatory B cells that suppress autoimmune disease
Open accessAbstract
Interleukin-10 (IL-10)-producing regulatory B (Breg) cells suppress autoimmune disease, and increased numbers of Breg cells prevent host defense to infection and promote tumor growth and metastasis by converting resting CD4+ T cells to regulatory T (Treg) cells. The mechanisms mediating the induction and development of Breg cells remain unclear. Here we show that IL-35 induces Breg cells and promotes their conversion to a Breg subset that produces IL-35 as well as IL-10. Treatment of mice with IL-35 conferred protection from experimental autoimmune uveitis (EAU), and mice lacking IL-35 (p35 knockout (KO) mice) or defective in IL-35 signaling (IL-12Rβ2 KO mice) produced less Breg cells endogenously or after treatment with IL-35 and developed severe uveitis. Adoptive transfer of Breg cells induced by recombinant IL-35 suppressed EAU when transferred to mice with established disease, inhibiting pathogenic T helper type 17 (TH17) and TH1 cells while promoting Treg cell expansion. In B cells, IL-35 activates STAT1 and STAT3 through the IL-35 receptor comprising the IL-12Rβ2 and IL-27Rα subunits. As IL-35 also induced the conversion of human B cells into Breg cells, these findings suggest that IL-35 may be used to induce autologous Breg and IL-35+ Breg cells and treat autoimmune and inflammatory disease.
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Metadata
- Authors
- Wang, R.-X., Yu, C.-R., Dambuza, I. M., Mahdi, R. M., Dolinska, M. B., Sergeev, Y. V., Wingfield, P. T., Kim, S.-H., & Egwuagu, C. E.
- Venue
- Nature Medicine
- Published
- 2014-04-17
- Volume
- 20
- Issue
- 6
- Pages
- 633-641
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1995112525
- Cited by
- 733
- References
- 44
- FWCI
- 26.32
- Type
- journal article
- Language
- en
- Open access
- green
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