TY - JOUR
T1 - γδ T cells compose a developmentally regulated intrauterine population and protect against vaginal candidiasis
AU - Monin, L.
AU - Ushakov, D. S.
AU - Arnesen, H.
AU - Bah, N.
AU - Jandke, A.
AU - Muñoz-Ruiz, M.
AU - Carvalho, J.
AU - Joseph, S.
AU - Almeida, B. C.
AU - Green, M. J.
AU - Nye, E.
AU - Hatano, S.
AU - Yoshikai, Y.
AU - Curtis, M.
AU - Carlsen, H.
AU - Steinhoff, U.
AU - Boysen, P.
AU - Hayday, A.
N1 - Funding Information:
We thank staff of the Francis Crick Institute (FCI) platforms for flow cytometry, advanced sequencing and BRF, and the Nikon Imaging Centre at KCL for expert assistance. We thank S. Gaffen, B. Coleman, A. Baulies, S. Domingos Cardoso Da Rocha, L. F. Moen, G. M. Johansen, and M. Charalambous for technical support and advice. The authors acknowledge Archer Immunoverse for TCR sequencing, and J. Naglik for C.albicans. The work was supported by: Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement #792383 (L.M.); Medical Research Council (MRC) (Grant award # MR/P012175/1 and MR/ P012175/2 (GF mice); a Wellcome Trust (WT) Investigator Award (106292/Z/14/Z) (A.H.); EMBO ALTF 198-2018 (M.M.-R.); NMBU (H.A., P.B., and H.C.) and the FCI, which receives core funding from Cancer Research UK (FC001093), the MRC (FC001093), and the WT (FC001093) (A.H.).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/11/1
Y1 - 2020/11/1
N2 - This most comprehensive analysis to date of γδ T cells in the murine uterus reveals them to compose a unique local T-cell compartment. Consistent with earlier reports, most cells expressed a canonical Vγ6Vδ1 TCR, and produced interleukin (IL)-17A upon stimulation. Nonetheless, contrasting with earlier reports, uterine γδ T cells were not obviously intraepithelial, being more akin to sub-epithelial Vγ6Vδ1+ T cells at several other anatomical sites. By contrast to other tissues however, the uterine compartment also included non-Vγ6+, IFN-γ-producing cells; was strikingly enriched in young mice; expressed genes hitherto associated with the uterus, including the progesterone receptor; and did not require microbes for development and/or maintenance. This notwithstanding, γδ T-cell deficiency severely impaired resistance to reproductive tract infection by Candida albicans, associated with decreased responses of IL-17-dependent neutrophils. These findings emphasise tissue-specific complexities of different mucosal γδ cell compartments, and their evident importance in lymphoid stress-surveillance against barrier infection.
AB - This most comprehensive analysis to date of γδ T cells in the murine uterus reveals them to compose a unique local T-cell compartment. Consistent with earlier reports, most cells expressed a canonical Vγ6Vδ1 TCR, and produced interleukin (IL)-17A upon stimulation. Nonetheless, contrasting with earlier reports, uterine γδ T cells were not obviously intraepithelial, being more akin to sub-epithelial Vγ6Vδ1+ T cells at several other anatomical sites. By contrast to other tissues however, the uterine compartment also included non-Vγ6+, IFN-γ-producing cells; was strikingly enriched in young mice; expressed genes hitherto associated with the uterus, including the progesterone receptor; and did not require microbes for development and/or maintenance. This notwithstanding, γδ T-cell deficiency severely impaired resistance to reproductive tract infection by Candida albicans, associated with decreased responses of IL-17-dependent neutrophils. These findings emphasise tissue-specific complexities of different mucosal γδ cell compartments, and their evident importance in lymphoid stress-surveillance against barrier infection.
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U2 - 10.1038/s41385-020-0305-7
DO - 10.1038/s41385-020-0305-7
M3 - Article
C2 - 32472066
AN - SCOPUS:85085693176
SN - 1933-0219
VL - 13
SP - 969
EP - 981
JO - Mucosal Immunology
JF - Mucosal Immunology
IS - 6
ER -