c-Maf enforces cytokine production and promotes memory-like responses in mouse and human type 2 innate lymphoid cells.
Fiche publication
Date publication
avril 2022
Journal
The EMBO journal
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier
Tous les auteurs :
Trabanelli S, Ercolano G, Wyss T, Gomez-Cadena A, Falquet M, Cropp D, Imbratta C, Leblond MM, Salvestrini V, Curti A, Adotevi O, Jandus C, Verdeil G
Lien Pubmed
Résumé
Group-2 innate lymphoid cells (ILC2s), which are involved in type 2 inflammatory diseases such as allergy, can exhibit immunological memory, but the basis of this ILC2 "trained immunity" has remained unclear. Here, we found that stimulation with IL-33/IL-25 or exposure to the allergen papain induces the expression of the transcription factor c-Maf in mouse ILC2s. Chronic papain exposure results in high production of IL-5 and IL-13 cytokines and lung eosinophil recruitment, effects that are blocked by c-Maf deletion in ILCs. Transcriptomic analysis revealed that knockdown of c-Maf in ILC2s suppresses expression of type 2 cytokine genes, as well as of genes linked to a memory-like phenotype. Consistently, c-Maf was found highly expressed in human adult ILC2s but absent in cord blood and required for cytokine production in isolated human ILC2s. Furthermore, c-Maf-deficient mouse or human ILC2s failed to exhibit strengthened ("trained") responses upon repeated challenge. Thus, the expression of c-Maf is indispensable for optimal type 2 cytokine production and proper memory-like responses in group-2 innate lymphoid cells.
Mots clés
ILC2, c-Maf, immune training, lung inflammation
Référence
EMBO J. 2022 Apr 25;:e109300