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Cell Mol Immunol. 2019 Apr 4. doi: 10.1038/s41423-019-0227-z. [Epub ahead of print]

IL-10-producing regulatory B cells restrain the T follicular helper cell response in primary Sjögren's syndrome.

Author information

1
Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China.
2
Department of Rheumatology and Immunology, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China.
3
Department of Rheumatology, Peking Union Medical College Hospital, Beijing, China.
4
Department of Rheumatology, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang, China.
5
Department of Rheumatology and Immunology, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China. liu_dz2001@sina.com.
6
Department of Rheumatology, Peking Union Medical College Hospital, Beijing, China. zhaoyan_pumch2002@aliyun.com.
7
Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China. liweilu@hku.hk.

Abstract

Increased 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.

KEYWORDS:

Breg cells; Primary Sjögren’s syndrome; T follicular helper cells

PMID:
30948793
DOI:
10.1038/s41423-019-0227-z

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