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IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease
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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620058/ https://www.ncbi.nlm.nih.gov/pubmed/28959012 http://dx.doi.org/10.1038/s41467-017-00838-4 |
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author | Dambuza, Ivy M. He, Chang Choi, Jin Kyeong Yu, Cheng-Rong Wang, Renxi Mattapallil, Mary J. Wingfield, Paul T. Caspi, Rachel R. Egwuagu, Charles E. |
author_facet | Dambuza, Ivy M. He, Chang Choi, Jin Kyeong Yu, Cheng-Rong Wang, Renxi Mattapallil, Mary J. Wingfield, Paul T. Caspi, Rachel R. Egwuagu, Charles E. |
author_sort | Dambuza, Ivy M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5620058 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56200582017-10-02 IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease Dambuza, Ivy M. He, Chang Choi, Jin Kyeong Yu, Cheng-Rong Wang, Renxi Mattapallil, Mary J. Wingfield, Paul T. Caspi, Rachel R. Egwuagu, Charles E. Nat Commun Article 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. Nature Publishing Group UK 2017-09-28 /pmc/articles/PMC5620058/ /pubmed/28959012 http://dx.doi.org/10.1038/s41467-017-00838-4 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Dambuza, Ivy M. He, Chang Choi, Jin Kyeong Yu, Cheng-Rong Wang, Renxi Mattapallil, Mary J. Wingfield, Paul T. Caspi, Rachel R. Egwuagu, Charles E. IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease |
title | IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease |
title_full | IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease |
title_fullStr | IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease |
title_full_unstemmed | IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease |
title_short | IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease |
title_sort | il-12p35 induces expansion of il-10 and il-35-expressing regulatory b cells and ameliorates autoimmune disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620058/ https://www.ncbi.nlm.nih.gov/pubmed/28959012 http://dx.doi.org/10.1038/s41467-017-00838-4 |
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