2. Academic Validation
  3. IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease

IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease

  • Nat Commun. 2017 Sep 28;8(1):719. doi: 10.1038/s41467-017-00838-4.
Ivy M Dambuza 1,  Chang He 1 2,  Jin Kyeong Choi 1,  Cheng-Rong Yu 1,  Renxi Wang 1 3,  Mary J Mattapallil 4,  Paul T Wingfield 5,  Rachel R Caspi 4,  Charles E Egwuagu 6
Affiliations

Affiliations

  • 1 Molecular Immunology Section, Laboratory of Immunology, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
  • 2 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, China.
  • 3 Laboratory of Immunology, Beijing Institute of Basic Medical Sciences, Beijing, 100850, China.
  • 4 Immunoregulation Section, Laboratory of Immunology, NEI, NIH, Bethesda, MD, 20892, USA.
  • 5 Protein Expression Laboratory, National Institute Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, MD, 20814, USA.
  • 6 Molecular Immunology Section, Laboratory of Immunology, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA. egwuaguc@nei.nih.gov.
PMID: 28959012 DOI: 10.1038/s41467-017-00838-4
Abstract

Interleukin 35 (IL-35) is a heterodimeric cytokine composed of IL-12p35 and Ebi3 subunits. IL-35 suppresses autoimmune diseases while preventing host defense to Infection and promoting tumor growth and metastasis by converting resting B and T cells into IL-10-producing and IL-35-producing regulatory B (Breg) and T (Treg) cells. Despite sharing the IL-12p35 subunit, IL-12 (IL-12p35/IL-12p40) promotes inflammatory responses whereas IL-35 (IL-12p35/Ebi3) induces regulatory responses, suggesting that IL-12p35 may have unknown intrinsic immune-regulatory functions regulated by its heterodimeric partner. Here we show that the IL-12p35 subunit has immunoregulatory functions hitherto attributed to IL-35. IL-12p35 suppresses lymphocyte proliferation, induces expansion of IL-10-expressing and IL-35-expressing B cells and ameliorates autoimmune uveitis in mice by antagonizing pathogenic Th17 responses. Recapitulation of essential immunosuppressive activities of IL-35 indicates that IL-12p35 may be utilized for in vivo expansion of Breg cells and autologous Breg cell immunotherapy. Furthermore, our uveitis data suggest that intrinsic immunoregulatory activities of other single chain IL-12 subunits might be exploited to treat other autoimmune diseases.IL-12p35 is common to IL-35 and IL-12, which have opposing effects on inflammation. Here the authors show that the IL-12p35 subunit induces regulatory B cells and can be used therapeutically to limit autoimmune uveitis in mice.

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