Intrinsic factors and CD1d1 but not CD1d2 expression levels control invariant natural killer T cell subset differentiation

Ludivine Amable (1) , Luis Antonio Ferreira Martins (1) , Remi Pierre (2) , Marcio Do Cruseiro (2) , Ghita Chabab (3) , Arnauld Sergé (4) , Camille Kergaravat (1) , Marc Delord (5) , Christophe Viret (6) , Jean Jaubert (7) , Chaohong Liu (8) , Saoussen Karray (9) , Julien C Marie (3) , Magali Irla (10) , Hristo Georgiev (11) , Emmanuel Clave (1) , Antoine Toubert (1) , Bruno Lucas (12) , Jihene Klibi (1) , Kamel Benlagha (1)

1 EMily (UMR_S_1160 / U1160) - Ecotaxie, microenvironnement et développement lymphocytaire
2 PRHTEC - Plateforme Recombinaison Homologue, Transfert d'Embryons et Cryoconservation [Institut Cochin]
3 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
4 LAI - Adhésion et Inflammation
5 King‘s College London
6 CIRI - Centre International de Recherche en Infectiologie
7 Génétique de la souris - Mouse Genetics
8 Tongji Medical College [HUST]
9 HIPI (UMR_S_976 / U976) - Immunologie humaine, physiopathologie & immunothérapie
10 CIML - Centre d'Immunologie de Marseille - Luminy
11 MHH - Medizinische Hochschule Hannover = Hannover Medical School
12 IC UM3 (UMR 8104 / U1016) - Institut Cochin

Invariant natural killer T (NKT) cell subsets are defined based on their cytokine-production profiles and transcription factors. Their distribution is different in C57BL/6 (B6) and BALB/c mice, with a bias for NKT1 and NKT2/NKT17 subsets, respectively. Here, we show that the non-classical class I-like major histocompatibility complex CD1 molecules CD1d2, expressed in BALB/c and not in B6 mice, could not account for this difference. We find however that NKT cell subset distribution is intrinsic to bone marrow derived NKT cells, regardless of syngeneic CD1d-ligand recognition, and that multiple intrinsic factors are likely involved. Finally, we find that CD1d expression levels in combination with T cell antigen receptor signal strength could also influence NKT cell distribution and function. Overall, this study indicates that CD1d-mediated TCR signals and other intrinsic signals integrate to influence strain-specific NKT cell differentiation programs and subset distributions.

Domaines: Immunologie

Ludivine Amable, Luis Antonio Ferreira Martins, Remi Pierre, Marcio Do Cruseiro, Ghita Chabab, et al.. Intrinsic factors and CD1d1 but not CD1d2 expression levels control invariant natural killer T cell subset differentiation. Nature Communications, 2023, 14 (1), pp.7922. ⟨10.1038/s41467-023-43424-7⟩. ⟨hal-04328475⟩