Runx/Cbfβ in cDC2s prime Rorγt+ T cells Mari Tenno, Alicia Yoke Wei Wong, Mika Ikegaya, Eiji Miyauchi, Wooseok Seo, Peter See, Tamotsu Kato, Takashi Taida, Michiko Ohno-Oishi, Hiroshi Ohno, Hideyuki Yoshida, Florent Ginhoux, Ichiro Taniuchi Life Science Alliance Dec 2019, 3 (1) e201900441; DOI: 10.26508/lsa.201900441
Acquired immune responses are initiated by activation of CD4+ helper T (Th) cells via recognition of antigens presented by conventional dendritic cells (cDCs). DCs instruct Th-cell polarization program into specific effector Th subset, which will dictate the type of immune responses. Hence, it is important to unravel how differentiation and/or activation of DC are linked with Th-cell–intrinsic mechanism that directs differentiation toward a specific effector Th subset. Here, we show that loss of Runx/Cbfβ transcription factors complexes during DC development leads to loss of CD103+CD11b+ cDC2s and alters characteristics of CD103−CD11b+ cDCs in the intestine, which was accompanied with impaired differentiation of Rorγt+ Th17 cells and type 3 Rorγt+ regulatory T cells. We also show that a Runx-binding enhancer in the Rorc gene is essential for T cells to integrate cDC-derived signals to induce Rorγt expression. These findings reveal that Runx/Cbfβ complexes play crucial and complementary roles in cDCs and Th cells to shape converging type 3 immune responses.
We thank N Yoza for cell sorting, M Kawasumi for technical help in histological analyses, and Y Taniguchi for mouse genotyping. This work was supported by Grants-in-Aid for Scientific Research (B) (19390118) from Japan Society for the Promotion of Science, the Grants-in-Aid for Scientific Research on Innovative Areas (17H05805) from the Ministry of Education, Culture, Sports, Science and Technology in Japan (I Taniuchi), by RIKEN Center for Integrative Medical Sciences Young Chief Investigators program (H Yoshida), and by an European Molecular Biology Organization, Young Investigator Programme, Singapore Immunology Network (SIgN) core funding, a Singapore National Research Foundation Senior Investigatorship (NRFI)
NRF2016NRF-NRFI001-02 (F Ginhoux).