Oral Presentation CD1-MR1 Workshop 2025

Lymph nodes harbor distinct MAIT cell populations with varying residency behaviors and locations (#38)

Victoria Remy 1 , Anne-Laure Le Gac 1 , Aurélie Darbois 1 , Anastasia Du Halgouet 1 , Hélène Bugaut 1 , François Legoux 1 2 , Rafael Paiva 1 , Olivier Lantz 1 3 4 , Marion Salou 1
  1. Institut Curie, Paris, FRANCE, France
  2. INSERM ERL1305, CNRS UMR6290,, Université de Rennes, Institut de Génétique & Développement de Rennes, Rennes, France
  3. Centre d'investigation Clinique en Biothérapie Gustave-Roussy Institut Curie (CIC-BT1428), Paris, France
  4. Laboratoire d'immunologie clinique, Institut Curie, Paris, France

MAIT (Mucosal associated Invariant T) cells are actors of tissue immunity with rapid effector functions. These cells are also detected in lymph nodes (LNs)1,2, possibly tailoring the adaptive immune response to the drained tissue3. Indeed, MAIT cell presence or activation in lung draining LNs correlates with increased antigen-specific B and T cell . Whether this holds true in different LNs and the underlying mechanisms are unclear. Here, we investigated the dynamics and functions of MAIT cells in skin (sd), lung (med) and gut (mes) draining LNs. Distinct subsets of MAIT cells were identified by flow cytometry: whereas sd and medLNs harbored predominantly MAIT17 (RORgt+) cells, mesLNs encompassed MAIT1 (Tbet+), MAIT1/17 (RORgt+Tbet+) and immature PLZF+Tbet-RORgt- MAIT cells. MAIT cell subset distribution in LNs mirrored that of the drained tissues, and secreted cytokines secretion matching the identified subsets. Analysis of Foxn1-Cre MR1Flox/Flox mouse strain validated their selection on MR1-expressing hematopoietic cells. scRNAseq analysis suggested that the transcriptional program of MAIT17 cells varied between different LNs as MAIT cells from sdLN expressed CCR6, a chemokine receptor associated with subcapsular sinus location. Flow cytometry identified CCR6+CD169+ MAIT cells in sdLNs (and MedLNs to a lesser extent), suggesting close contact with CD169+ subcapsular macrophages, which prevent systemic spreading of pathogens. In situ hybridization using the MAIT TRAV sequence confirmed subcapsular location in sd and medLNs, and in the interfollicular or the T cell zone. MesLN MAIT cells were almost exclusively in the T cell zone. Strikingly, LN MAIT cells expressed a residency program particularly in the med and mesLN, which was validated by parabiosis experiments. These data suggest that LN MAIT cells have different programs and locations depending on the LN where they reside. Therefore, we are currently characterizing these programs and interrogating the specific functions in the different LNs.

 

  1. 1) Role of MR1-driven signals and amphiregulin on the recruitment and repair function of MAIT cells during skin wound healing, Du Halgouet et al. 2022, Immunity
  2. 2) A subset of follicular helper-like MAIT cells can provide B cell help and support antibody production in the mucosa , Jensen et al. 2022, Science Immunology
  3. 3) Lymphatic migration of unconventional T cells promotes site-specific immunity in distinct lymph nodes, Ataide et al. 2022, Immunity
  4. 4) MAIT cell activation augments adenovirus vector vaccine immunogenicity, Provine et al. 2021, Science
  5. 5) MAIT cells activate dendritic cells to promote TFH cell differentiation and induce humoral immunity, Pankhurst et al. 2023, Cell reports