c-Maf enforces cytokine production and promotes memory-like responses in mouse and human type 2 innate lymphoid cells

Article Article scientifique Article c-Maf enforces cytokine production and promotes memory-like responses in mouse and human type 2 innate lymphoid cells eng 2022-04-25 2022-04-25 author Trabanelli Sara 932754 author Ercolano Giuseppe 0000-0001-6026-2588 932440 author Wyss Tania 926481 author Gomez Cadena Alejandra 934607 author Falquet Maryline 932439 author Cropp Daniela author Imbratta Claire author Leblond Marine M author Salvestrini Valentina author Curti Antonio author Adotevi Olivier author Jandus Camilla 0000-0002-7405-5747 932821 author Verdeil Grégory e109300 10.15252/embj.2021109300 35467036 0261-4189 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. ILC2 C-Maf Immune training Lung inflammation Dewey 616.07 true 1309 Ciblage des lymphocytes sécrétant des cytokines 1015 EMBO journal 6bb34b59-3fe2-46d0-b35d-e688de08beeb Article (Published version) Public TrabanelliEMBO.pdf 1847769 application/pdf CC BY-NC-ND-4.0 openAccess

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c-Maf enforces cytokine production and promotes memory-like responses in mouse and human type 2 innate lymphoid cells	EMBO journal			2022	294	221

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Wyss, Tania