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Immunity. 2014 Dec 18;41(6):1040-51. doi: 10.1016/j.immuni.2014.10.016. Epub 2014 Nov 4.

Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation.

Author information

1
Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa 230-0045, Japan.
2
Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
3
Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
4
Laboratory for Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
5
Department of Advanced Medical Initiatives, JST-CREST, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
6
Laboratory for Immune Regulation, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
7
The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3050, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
8
Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa 230-0045, Japan. Electronic address: kurosaki@ifrec.osaka-u.ac.jp.
9
Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa 230-0045, Japan. Electronic address: babay@ifrec.osaka-u.ac.jp.

Abstract

B cells can suppress autoimmunity by secreting interleukin-10 (IL-10). Although subpopulations of splenic B lineage cells are reported to express IL-10 in vitro, the identity of IL-10-producing B cells with regulatory function in vivo remains unknown. By using IL-10 reporter mice, we found that plasmablasts in the draining lymph nodes (dLNs), but not splenic B lineage cells, predominantly expressed IL-10 during experimental autoimmune encephalomyelitis (EAE). These plasmablasts were generated only during EAE inflammation. Mice lacking plasmablasts by genetic ablation of the transcription factors Blimp1 or IRF4 in B lineage cells developed an exacerbated EAE. Furthermore, IRF4 positively regulated IL-10 production that can inhibit dendritic cell functions to generate pathogenic T cells. Our data demonstrate that plasmablasts in the dLNs serve as IL-10 producers to limit autoimmune inflammation and emphasize the importance of plasmablasts as IL-10-producing regulatory B cells.

PMID:
25484301
DOI:
10.1016/j.immuni.2014.10.016
[Indexed for MEDLINE]
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