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

Masanori Matsumoto, Akemi Baba, Takafumi Yokota, Hiroyoshi Nishikawa, Yasuyuki Ohkawa, Hisako Kayama, Axel Kallies, Stephen L. Nutt, Shimon Sakaguchi, Kiyoshi Takeda, Tomohiro Kurosaki, Yoshihiro Baba

Research output: Contribution to journalArticle

196 Citations (Scopus)

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 invitro, the identity of IL-10-producing B cells with regulatory function invivo 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 Tcells. 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.

Original languageEnglish
Pages (from-to)1040-1051
Number of pages12
JournalImmunity
Volume41
Issue number6
DOIs
Publication statusPublished - Dec 18 2014

Fingerprint

Interleukin-10
Inflammation
Autoimmune Experimental Encephalomyelitis
Regulatory B-Lymphocytes
Lymph Nodes
Genetic Transcription
Autoimmunity
Dendritic Cells
B-Lymphocytes
Transcription Factors

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation. / Matsumoto, Masanori; Baba, Akemi; Yokota, Takafumi; Nishikawa, Hiroyoshi; Ohkawa, Yasuyuki; Kayama, Hisako; Kallies, Axel; Nutt, Stephen L.; Sakaguchi, Shimon; Takeda, Kiyoshi; Kurosaki, Tomohiro; Baba, Yoshihiro.

In: Immunity, Vol. 41, No. 6, 18.12.2014, p. 1040-1051.

Research output: Contribution to journalArticle

Matsumoto, M, Baba, A, Yokota, T, Nishikawa, H, Ohkawa, Y, Kayama, H, Kallies, A, Nutt, SL, Sakaguchi, S, Takeda, K, Kurosaki, T & Baba, Y 2014, 'Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation', Immunity, vol. 41, no. 6, pp. 1040-1051. https://doi.org/10.1016/j.immuni.2014.10.016
Matsumoto, Masanori ; Baba, Akemi ; Yokota, Takafumi ; Nishikawa, Hiroyoshi ; Ohkawa, Yasuyuki ; Kayama, Hisako ; Kallies, Axel ; Nutt, Stephen L. ; Sakaguchi, Shimon ; Takeda, Kiyoshi ; Kurosaki, Tomohiro ; Baba, Yoshihiro. / Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation. In: Immunity. 2014 ; Vol. 41, No. 6. pp. 1040-1051.
@article{12cd5deeae6046f4b6453e15237c8a74,
title = "Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation",
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 invitro, the identity of IL-10-producing B cells with regulatory function invivo 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 Tcells. 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.",
author = "Masanori Matsumoto and Akemi Baba and Takafumi Yokota and Hiroyoshi Nishikawa and Yasuyuki Ohkawa and Hisako Kayama and Axel Kallies and Nutt, {Stephen L.} and Shimon Sakaguchi and Kiyoshi Takeda and Tomohiro Kurosaki and Yoshihiro Baba",
year = "2014",
month = "12",
day = "18",
doi = "10.1016/j.immuni.2014.10.016",
language = "English",
volume = "41",
pages = "1040--1051",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation

AU - Matsumoto, Masanori

AU - Baba, Akemi

AU - Yokota, Takafumi

AU - Nishikawa, Hiroyoshi

AU - Ohkawa, Yasuyuki

AU - Kayama, Hisako

AU - Kallies, Axel

AU - Nutt, Stephen L.

AU - Sakaguchi, Shimon

AU - Takeda, Kiyoshi

AU - Kurosaki, Tomohiro

AU - Baba, Yoshihiro

PY - 2014/12/18

Y1 - 2014/12/18

N2 - B cells can suppress autoimmunity by secreting interleukin-10 (IL-10). Although subpopulations of splenic B lineage cells are reported to express IL-10 invitro, the identity of IL-10-producing B cells with regulatory function invivo 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 Tcells. 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.

AB - B cells can suppress autoimmunity by secreting interleukin-10 (IL-10). Although subpopulations of splenic B lineage cells are reported to express IL-10 invitro, the identity of IL-10-producing B cells with regulatory function invivo 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 Tcells. 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.

UR - http://www.scopus.com/inward/record.url?scp=84918559452&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84918559452&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2014.10.016

DO - 10.1016/j.immuni.2014.10.016

M3 - Article

C2 - 25484301

AN - SCOPUS:84918559452

VL - 41

SP - 1040

EP - 1051

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 6

ER -