CD4+ Th2 cells are directly regulated by IL-10 during allergic airway inflammation
journal contributionposted on 12.08.2020, 11:30 by SM Coomes, Y Kannan, VS Pelly, LJ Entwistle, R Guidi, J Perez-Lloret, N Nikolov, W Müller, MS Wilson
Interleukin-10 (IL-10) is an important regulatory cytokine required to control allergy and asthma. IL-10-mediated regulation of T cell-mediated responses was previously thought to occur indirectly via antigen-presenting cells. However, IL-10 can act directly on regulatory T cells and T helper type 17 (Th17) cells. In the context of allergy, it is therefore unclear whether IL-10 can directly regulate T helper type 2 (Th2) cells and whether this is an important regulatory axis during allergic responses. We sought to determine whether IL-10 signaling in CD4+ Th2 cells was an important mechanism of immune regulation during airway allergy. We demonstrate that IL-10 directly limits Th2 cell differentiation and survival in vitro and in vivo. Ablation of IL-10 signaling in Th2 cells led to enhanced Th2 cell survival and exacerbated pulmonary inflammation in a murine model of house dust mite allergy. Mechanistically, IL-10R signaling regulated the expression of several genes in Th2 cells, including granzyme B. Indeed, IL-10 increased granzyme B expression in Th2 cells and led to increased Th2 cell death, identifying an IL-10-regulated granzyme B axis in Th2 cells controlling Th2 cell survival. This study provides clear evidence that IL-10 exerts direct effects on Th2 cells, regulating the survival of Th2 cells and severity of Th2-mediated allergic airway inflammation.
AnimalsAntigens, DermatophagoidesCell DifferentiationCell SurvivalCells, CulturedDisease Models, AnimalFemaleGranzymesHumansHypersensitivityImmune ToleranceInterleukin-10Lymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutPyroglyphidaeReceptors, Interleukin-10Signal TransductionTh2 CellsWilson FC001220FC-ackBRF-ackAS-ackHP-ackImmunology06 Biological Sciences11 Medical and Health Sciences