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
N1 - Funding Information:
We thank T. Okada for Bcl6 yfp/yfp mice; E. Hobeika and M. Reth for Mb1 Cre/+ mice; T. Matsuyama and K. Yui for Irf4 −/− mice; Y. Nakatsuji and T. Okuno for discussion; and P.W. Kincade for critical reading and editing of the manuscript. This work was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan (T.K., M.M., and Y.B.), Japan Science and Technology Agency and Core Research for Evolutional Science and Technology (T.K.), and Daiichi Sankyo Foundation of Life Science (Y.B.), and by grants and fellowships from the National Health and Medical Research Council of Australia (A.K. and S.L.N.), the Australia Research Council (A.K. and S.L.N.), and the Sylvia and Charles Viertel Foundation (A.K.) and was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIIS .
Publisher Copyright:
© 2014 Elsevier Inc.
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.
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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 -
