IRF4 expression by lung dendritic cells drives acute but not Trm cell–dependent memory Th2 responses
Abstract
Expression of the transcription factor interferon regulatory factor 4 (IRF4) is required for the development of lung conventional DCs type 2 (cDC2s) that elicit Th2 responses, yet how IRF4 functions in lung cDC2s throughout the acute and memory allergic response is not clear. Here, we used a mouse model that loses IRF4 expression after lung cDC2 development to demonstrate that mice with IRF4-deficient DCs display impaired memory responses to allergen. This defect in the memory response was a direct result of ineffective Th2 induction and impaired recruitment of activated effector T cells to the lung after sensitization. IRF4-deficient DCs demonstrated defects in their migration to the draining lymph node and in T cell priming. Finally, T cells primed by IRF4-competent DCs mediated potent memory responses independently of IRF4-expressing DCs, demonstrating that IRF4-expressing DCs are not necessary during the memory response. Thus, IRF4 controlled a program in mature DCs governing Th2 priming and effector responses, but IRF4-expressing DCs were dispensable during tissue-resident memory T cell–dependent memory responses.
Authors
Daniel F. Camacho, Tania E. Velez, Maile K. Hollinger, Esther Wang, Chanie L. Howard, Eli P. Darnell, Domenick E. Kennedy, Paulette A. Krishack, Cara L. Hrusch, Marcus R. Clark, James J. Moon, Anne I. Sperling
Figure 4
IRF4 regulates allergen phagocytosis and migration of CD24+ cDC2s to the lung draining lymph nodes during HDM sensitization.
