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Article: IL-10-producing regulatory B cells restrain the T follicular helper cell response in primary Sjögren’s syndrome

TitleIL-10-producing regulatory B cells restrain the T follicular helper cell response in primary Sjögren’s syndrome
Authors
KeywordsBreg cells
Primary Sjögren’s syndrome
T follicular helper cells
Issue Date2019
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/cmi/index.html
Citation
Cellular & Molecular Immunology, 2019, v. 16 n. 12, p. 921-931 How to Cite?
AbstractIncreased numbers of T follicular helper (Tfh) cells have been implicated in the development of autoimmune diseases including primary Sjögren’s syndrome (pSS), but how the Tfh cell response is regulated during autoimmune pathogenesis remains largely unclear. Here, we first found negative correlations between IL-10+ regulatory B (Breg) cell numbers and Tfh cell responses and disease activity in patients with pSS and mice with experimental Sjögren’s syndrome (ESS). Moreover, we detected high expression of IL-10 receptor on Tfh cells and their precursors in both humans and mice. In culture, IL-10 suppressed human and murine Tfh cell differentiation by promoting STAT5 phosphorylation. By using an adoptive transfer approach and two-photon live imaging, we found significantly increased numbers of Tfh cells with enhanced T cell homing into B cell follicles in the draining cervical lymph nodes of RAG-2−/− mice transferred with IL-10-deficient B cells during ESS development compared with those of RAG-2−/− mice transferred with wild-type B cells. In ESS mice, CD19+CD1dhiCD5+ Breg cells with decreased IL-10 production exhibited severely impaired suppressive effects on T cell proliferation. Consistently, CD19+CD24+CD38hi Breg cells from pSS patients showed significantly reduced IL-10 production with defective inhibitory function in the suppression of autologous Tfh cell expansion. Furthermore, the adoptive transfer of IL-10-producing Breg cells markedly suppressed the Tfh cell response and ameliorated ESS progression in ESS mice. Together, these findings demonstrate a critical role for IL-10-producing Breg cells in restraining the effector Tfh cell response during pSS development.
Persistent Identifierhttp://hdl.handle.net/10722/273014
ISSN
2019 Impact Factor: 8.484
2015 SCImago Journal Rankings: 1.898
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLin, X-
dc.contributor.authorWang, X-
dc.contributor.authorXiao, F-
dc.contributor.authorMa, K-
dc.contributor.authorLiu, L-
dc.contributor.authorWang, X-
dc.contributor.authorXu, D-
dc.contributor.authorWang, F-
dc.contributor.authorShi, X-
dc.contributor.authorLiu, D-
dc.contributor.authorZhao, Y-
dc.contributor.authorLu, L-
dc.date.accessioned2019-08-06T09:20:55Z-
dc.date.available2019-08-06T09:20:55Z-
dc.date.issued2019-
dc.identifier.citationCellular & Molecular Immunology, 2019, v. 16 n. 12, p. 921-931-
dc.identifier.issn1672-7681-
dc.identifier.urihttp://hdl.handle.net/10722/273014-
dc.description.abstractIncreased numbers of T follicular helper (Tfh) cells have been implicated in the development of autoimmune diseases including primary Sjögren’s syndrome (pSS), but how the Tfh cell response is regulated during autoimmune pathogenesis remains largely unclear. Here, we first found negative correlations between IL-10+ regulatory B (Breg) cell numbers and Tfh cell responses and disease activity in patients with pSS and mice with experimental Sjögren’s syndrome (ESS). Moreover, we detected high expression of IL-10 receptor on Tfh cells and their precursors in both humans and mice. In culture, IL-10 suppressed human and murine Tfh cell differentiation by promoting STAT5 phosphorylation. By using an adoptive transfer approach and two-photon live imaging, we found significantly increased numbers of Tfh cells with enhanced T cell homing into B cell follicles in the draining cervical lymph nodes of RAG-2−/− mice transferred with IL-10-deficient B cells during ESS development compared with those of RAG-2−/− mice transferred with wild-type B cells. In ESS mice, CD19+CD1dhiCD5+ Breg cells with decreased IL-10 production exhibited severely impaired suppressive effects on T cell proliferation. Consistently, CD19+CD24+CD38hi Breg cells from pSS patients showed significantly reduced IL-10 production with defective inhibitory function in the suppression of autologous Tfh cell expansion. Furthermore, the adoptive transfer of IL-10-producing Breg cells markedly suppressed the Tfh cell response and ameliorated ESS progression in ESS mice. Together, these findings demonstrate a critical role for IL-10-producing Breg cells in restraining the effector Tfh cell response during pSS development.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/cmi/index.html-
dc.relation.ispartofCellular & Molecular Immunology-
dc.subjectBreg cells-
dc.subjectPrimary Sjögren’s syndrome-
dc.subjectT follicular helper cells-
dc.titleIL-10-producing regulatory B cells restrain the T follicular helper cell response in primary Sjögren’s syndrome-
dc.typeArticle-
dc.identifier.emailLin, X: linxiang@hku.hk-
dc.identifier.emailWang, X: xiaohuiwang@hku.hk-
dc.identifier.emailXiao, F: xiaof@hku.hk-
dc.identifier.emailMa, K: kongyang@hku.hk-
dc.identifier.emailLu, L: liweilu@hku.hk-
dc.identifier.authorityLin, X=rp02623-
dc.identifier.authorityWang, X=rp02664-
dc.identifier.authorityLu, L=rp00477-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/s41423-019-0227-z-
dc.identifier.pmid30948793-
dc.identifier.pmcidPMC6884445-
dc.identifier.scopuseid_2-s2.0-85063937862-
dc.identifier.hkuros300598-
dc.identifier.volume16-
dc.identifier.issue12-
dc.identifier.spage921-
dc.identifier.epage931-
dc.identifier.isiWOS:000500266900004-
dc.publisher.placeChina-

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