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
IMMUNITY | CELL PRESS | Published : 2014
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 regu..View full abstract
Awarded by Grants-in-Aid for Scientific Research
We thank T. Okada for Bcl6<SUP>yfp/yfp</SUP> mice; E. Hobeika and M. Reth for Mb1<SUP>Cre/+</SUP> mice; T. Matsuyama and K. Yui for Irf4<SUP>-/-</SUP> 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.