Surgery (RMH) - Research Publications

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Author: Belz, Gabrielle × Author: Putoczki, Tracy × Author: Shi, Wei × End date: 2019 ×

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    Complementarity and redundancy of IL-22-producing innate lymphoid cells
    Rankin, LC ; Girard-Madoux, MJH ; Seillet, C ; Mielke, LA ; Kerdiles, Y ; Fenis, A ; Wieduwild, E ; Putoczki, T ; Mondot, S ; Lantz, O ; Demon, D ; Papenfuss, AT ; Smyth, GK ; Lamkanfi, M ; Carotta, S ; Renauld, J-C ; Shi, W ; Carpentier, S ; Soos, T ; Arendt, C ; Ugolini, S ; Huntington, ND ; Bez, GT ; Vivier, E (NATURE PUBLISHING GROUP, 2016-02)
    Intestinal T cells and group 3 innate lymphoid cells (ILC3 cells) control the composition of the microbiota and gut immune responses. Within the gut, ILC3 subsets coexist that either express or lack the natural cytoxicity receptor (NCR) NKp46. We identified here the transcriptional signature associated with the transcription factor T-bet-dependent differentiation of NCR(-) ILC3 cells into NCR(+) ILC3 cells. Contrary to the prevailing view, we found by conditional deletion of the key ILC3 genes Stat3, Il22, Tbx21 and Mcl1 that NCR(+) ILC3 cells were redundant for the control of mouse colonic infection with Citrobacter rodentium in the presence of T cells. However, NCR(+) ILC3 cells were essential for cecal homeostasis. Our data show that interplay between intestinal ILC3 cells and adaptive lymphocytes results in robust complementary failsafe mechanisms that ensure gut homeostasis.
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    TCF-1 limits the formation of Tc17 cells via repression of the MAF-RORγt axis
    Mielke, LA ; Liao, Y ; Clemens, EB ; Firth, MA ; Duckworth, B ; Huang, Q ; Almeida, FF ; Chopin, M ; Koay, H-F ; Bell, CA ; Hediyeh-Zadeh, S ; Park, SL ; Raghu, D ; Choi, J ; Putoczki, TL ; Hodgkin, PD ; Franks, AE ; Mackay, LK ; Godfrey, D ; Davis, MJ ; Xue, H-H ; Bryant, VL ; Kedzierska, K ; Shi, W ; Belz, GT (ROCKEFELLER UNIV PRESS, 2019-07)
    Interleukin (IL)-17-producing CD8+ T (Tc17) cells have emerged as key players in host-microbiota interactions, infection, and cancer. The factors that drive their development, in contrast to interferon (IFN)-γ-producing effector CD8+ T cells, are not clear. Here we demonstrate that the transcription factor TCF-1 (Tcf7) regulates CD8+ T cell fate decisions in double-positive (DP) thymocytes through the sequential suppression of MAF and RORγt, in parallel with TCF-1-driven modulation of chromatin state. Ablation of TCF-1 resulted in enhanced Tc17 cell development and exposed a gene set signature to drive tissue repair and lipid metabolism, which was distinct from other CD8+ T cell subsets. IL-17-producing CD8+ T cells isolated from healthy humans were also distinct from CD8+IL-17- T cells and enriched in pathways driven by MAF and RORγt Overall, our study reveals how TCF-1 exerts central control of T cell differentiation in the thymus by normally repressing Tc17 differentiation and promoting an effector fate outcome.