Role of MR1-driven signals and amphiregulin on the recruitment and repair function of MAIT cells during skin wound healing

Anastasia Du Halgouet (1) , Aurélie Darbois (1) , Mansour Alkobtawi (2) , Martin Mestdagh (1) , Aurélia Alphonse (1) , Virginie Premel (1) , Thomas Yvorra (3) , Ludovic Colombeau (3) , Raphaël Rodriguez (3) , Dietmar Zaiss (4, 5, 6) , Yara El Morr (1) , Hélène Bugaut (1) , François Legoux (1) , Laetitia Perrin (1) , Selim Aractingi (2) , Rachel Golub (7) , Olivier Lantz (1, 8, 9) , Marion Salou (1)

1 U932 - Immunité et cancer
2 IC UM3 (UMR 8104 / U1016) - Institut Cochin
3 CBMCT - UMR 3666 / U1143 - Chimie biologique des membranes et ciblage thérapeutique
4 UR - Universität Regensburg
5 University Hospital Regensburg
6 Leibniz Institute of Immunotherapy - University of Regensburg
7 Lymphocytes et Immunité - Lymphocytes and Immunity
8 Institut Curie [Paris]
9 CIC 1428 , CBT 507 - Centre d'Investigation Clinique en Biotherapie des cancers

Tissue repair processes maintain proper organ function following mechanical or infection-related damage. In addition to antibacterial properties, mucosal associated invariant T (MAIT) cells express a tissue repair transcriptomic program and promote skin wound healing when expanded. Herein, we use a human-like mouse model of full-thickness skin excision to assess the underlying mechanisms of MAIT cell tissue repair function. Single-cell RNA sequencing analysis suggested that skin MAIT cells already express a repair program at steady state. Following skin excision, MAIT cells promoted keratinocyte proliferation, thereby accelerating healing. Using skin grafts, parabiosis, and adoptive transfer experiments, we show that MAIT cells migrated into the wound in a T cell receptor (TCR)-independent but CXCR6 chemokine receptor-dependent manner. Amphiregulin secreted by MAIT cells following excision promoted wound healing. Expression of the repair function was probably independent of sustained TCR stimulation. Overall, our study provides mechanistic insights into MAIT cell wound healing function in the skin.

Keywords: CXCR6 chemokine receptor; MAIT cells; TCR signaling; amphiregulin; scRNA-seq; skin excision; tissue repair

Domains: Life Sciences [q-bio]

Anastasia Du Halgouet, Aurélie Darbois, Mansour Alkobtawi, Martin Mestdagh, Aurélia Alphonse, et al.. Role of MR1-driven signals and amphiregulin on the recruitment and repair function of MAIT cells during skin wound healing. Immunity, 2023, 56 (1), pp.78-92.e6. ⟨10.1016/j.immuni.2022.12.004⟩. ⟨pasteur-03956120⟩