A divergent transcriptional landscape underpins the development and functional branching of MAIT cells

Koay, HF; Su, S; Amann-Zalcenstein, D; Daley, SR; Comerford, I; Miosge, L; Whyte, CE; Konstantinov, IE; d&#39;Udekem, Y; Baldwin, T; Hickey, PF; Berzins, SP; Mak, JYW; Sontani, Y; Roots, CM; Sidwell, T; Kallies, A; Chen, Z; Nussing, S; Kedzierska, K; Mackay, LK; McColl, SR; Deenick, EK; Fairlie, DP; McCluskey, J; Goodnow, CC; Ritchie, ME; Belz, GT; Naik, SH; Pellicci, DG; Godfrey, DI

Author(s): Koay, HF; Su, S; Amann-Zalcenstein, D; Daley, SR; Comerford, I; Miosge, L; Whyte, CE; Konstantinov, IE; d'Udekem, Y; Baldwin, T; Hickey, PF; Berzins, SP; Mak, JYW; Sontani, Y; Roots, CM; Sidwell, T; Kallies, A; Chen, Z; Nussing, S; Kedzierska, K; Mackay, LK; McColl, SR; Deenick, EK; Fairlie, DP; McCluskey, J; Goodnow, CC; Ritchie, ME; Belz, GT; Naik, SH; Pellicci, DG; Godfrey, DI;
Details: Publication Year 2019-11-22,Volume 4,Issue #41,Page pii: eaay6039
Journal Title: Science Immunology
Publication Type: Journal Article
Abstract: MR1-restricted mucosal-associated invariant T (MAIT) cells play a unique role in the immune system. These cells develop intrathymically through a three-stage process, but the events that regulate this are largely unknown. Here, using bulk and single-cell RNA sequencing-based transcriptomic analysis in mice and humans, we studied the changing transcriptional landscape that accompanies transition through each stage. Many transcripts were sharply modulated during MAIT cell development, including SLAM (signaling lymphocytic activation molecule) family members, chemokine receptors, and transcription factors. We also demonstrate that stage 3 "mature" MAIT cells comprise distinct subpopulations including newly arrived transitional stage 3 cells, interferon-gamma-producing MAIT1 cells and interleukin-17-producing MAIT17 cells. Moreover, the validity and importance of several transcripts detected in this study are directly demonstrated using specific mutant mice. For example, MAIT cell intrathymic maturation was found to be halted in SLAM-associated protein (SAP)-deficient and CXCR6-deficient mouse models, providing clear evidence for their role in modulating MAIT cell development. These data underpin a model that maps the changing transcriptional landscape and identifies key factors that regulate the process of MAIT cell differentiation, with many parallels between mice and humans.
Publisher: AAAS
Research Division(s): Epigenetics And Development; Immunology; Blood Cells And Blood Cancer
PubMed ID: 31757835
Publisher's Version: https://doi.org/10.1126/sciimmunol.aay6039
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2019-12-05 01:26:20

Last Modified: 2019-12-05 01:59:23