Proinflammatory Stimuli Induce The Generation Of IL-17-producing TH2 Memory Cells That Is Associated With Exacerbated Allergic Diseases
RATIONALE: IL-17-producing CD4+ T cells are shown to play important role in inducing neutrophilic inflammation in acute airway inflammation. However, the identity and roles of IL-17-producing CD4+ T cells in inducing TH2-biased chronic allergic inflammation remain unclear. METHODS: Immunofluorscence and RT-PCR analyses were employed to characterize two subsets of CRTH2+CD4+ TH2 memory cells. In allergen-challenged animal model, ovalbumin or ovalbumin plus Aspergillus oryzae were administrated intranasally to IL-4/GFP mice, TH2 effector/memory cells were isolated from tissues and analyzed by immunofluorscence analyses. RESULTS: CRTH2-expressing CD4+ T cells are shown to be memory T cells with Th2 characteristics. Here, we report that CRTH2+CD4+ TH2 memory cells could be divided into two subsets based on their surface CCR6 expression. Remarkably, purified CRTH2+CCR6+ TH2 memory cells are capable of producing proinflammatory cytokine IL-17A, together with other TH2 cytokines, whereas CRTH2+CCR6- TH2 memory cells can only produce TH2 cytokines. Moreover, CRTH2+CCR6+ TH2 memory cells express both GATA-3 and ROR947;t transcripts, the transcription factors known to be master regulator of TH2 and TH17 respectively. Proinflammatory cytokines, such as IL-1946;, IL-6, TGF-946;, are capable of inducing IL-17 production by CRTH2+CCR68722; TH2 memory cells. In allergen-challenged mouse models, IL-17-producing TH2 effector/memory cells were found to be dominant in the inflamed lung, but not other lymphoid tissues. CONCLUSIONS: These findings demonstrate that the generation of IL-17-producing TH2 memory/effector T cells can occur in the complex inflammatory microenvironments at mucosal tissues during allergic inflammation both in human and mouse.
Full conference title:
American Academy of Allergy Asthma & Immunology