TY - JOUR
T1 - A common transcriptomic program acquired in the thymus defines tissue residency of MAIT and NKT subsets
AU - Salou, Marion
AU - Legoux, François
AU - Gilet, Jules
AU - Darbois, Aurélie
AU - Du Halgouet, Anastasia
AU - Alonso, Ruby
AU - Richer, Wilfrid
AU - Goubet, Anne Gaëlle
AU - Daviaud, Céline
AU - Menger, Laurie
AU - Procopio, Emanuele
AU - Premel, Virginie
AU - Lantz, Olivier
N1 - Publisher Copyright:
© 2018 Salou et al.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Mucosal-associated invariant T (MAIT) cells are abundant T cells with unique specificity for microbial metabolites. MAIT conservation along evolution indicates important functions, but their low frequency in mice has hampered their detailed characterization. Here, we performed the first transcriptomic analysis of murine MAIT cells. MAIT1 (RORγtneg) and MAIT17 (RORγt + ) subsets were markedly distinct from mainstream T cells, but quasi-identical to NKT1 and NKT17 subsets. The expression of similar programs was further supported by strong correlations of MAIT and NKT frequencies in various organs. In both mice and humans, MAIT subsets expressed gene signatures associated with tissue residency. Accordingly, parabiosis experiments demonstrated that MAIT and NKT cells are resident in the spleen, liver, and lungs, with LFA1/ ICAM1 interactions controlling MAIT1 and NKT1 retention in spleen and liver. The transcriptional program associated with tissue residency was already expressed in thymus, as confirmed by adoptive transfer experiments. Altogether, shared thymic differentiation processes generate “preset” NKT and MAIT subsets with defined effector functions, associated with specific positioning into tissues.
AB - Mucosal-associated invariant T (MAIT) cells are abundant T cells with unique specificity for microbial metabolites. MAIT conservation along evolution indicates important functions, but their low frequency in mice has hampered their detailed characterization. Here, we performed the first transcriptomic analysis of murine MAIT cells. MAIT1 (RORγtneg) and MAIT17 (RORγt + ) subsets were markedly distinct from mainstream T cells, but quasi-identical to NKT1 and NKT17 subsets. The expression of similar programs was further supported by strong correlations of MAIT and NKT frequencies in various organs. In both mice and humans, MAIT subsets expressed gene signatures associated with tissue residency. Accordingly, parabiosis experiments demonstrated that MAIT and NKT cells are resident in the spleen, liver, and lungs, with LFA1/ ICAM1 interactions controlling MAIT1 and NKT1 retention in spleen and liver. The transcriptional program associated with tissue residency was already expressed in thymus, as confirmed by adoptive transfer experiments. Altogether, shared thymic differentiation processes generate “preset” NKT and MAIT subsets with defined effector functions, associated with specific positioning into tissues.
UR - http://www.scopus.com/inward/record.url?scp=85059928700&partnerID=8YFLogxK
U2 - 10.1084/jem.20181483
DO - 10.1084/jem.20181483
M3 - Article
C2 - 30518599
AN - SCOPUS:85059928700
SN - 0022-1007
VL - 216
SP - 133
EP - 151
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 1
ER -