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Nat Med. 2014 Jun;20(6):633-41. doi: 10.1038/nm.3554. Epub 2014 Apr 17.

Interleukin-35 induces regulatory B cells that suppress autoimmune disease.

Author information

1
1] Molecular Immunology Section, Laboratory of Immunology, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, Maryland, USA. [2] Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
2
Molecular Immunology Section, Laboratory of Immunology, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
3
Ophthalmic Genetics and Visual Functions Branch, NEI, NIH, Bethesda, Maryland, USA.
4
Protein Expression Laboratory, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, USA.

Erratum in

  • Nat Med. 2014 Jun;20(6). doi: 10.1038/nm.3554.

Abstract

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.

PMID:
24743305
PMCID:
PMC4048323
DOI:
10.1038/nm.3554
[Indexed for MEDLINE]
Free PMC Article

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