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Activation of Th cells gives rise to various subsets of effector cells that are controlled via specialised regulatory T cells or through self\u2010regulation via production of IL\u201010. However, the environmental factors that regulate IL\u201010 production by Th cells remain poorly understood. Here, we show that the neurotrophic factor receptor rearranged during transfection (RET) downregulates IL\u201010 production by Th cells from C57BL\/6 mice. We found that effector Th cells express RET and that RET's neurotrophic factor partners are mainly produced by LN stromal cells, allowing context\u2010dependent Th\u2010cell regulation. Despite being dispensable for Th\u2010cell homeostasis, RET controls IL\u201010 production in Th2 cells: RET\u2010deficient Th cells exhibited increased IL\u201010 production, while triggering of Th1\/2 cells with neurotrophic factors, namely glial\u2010derived neurotrophic factor and neurturin, decreased the expression of IL\u201010. In agreement, the important IL\u201010 transcription factor <jats:italic>Maf<\/jats:italic> was upregulated in RET\u2010deficient Th2 cells and down\u2010regulated upon RET signalling activation by glial\u2010derived neurotrophic factor family ligands. Thus, our study uncovers neurotrophic factors as novel regulators of Th\u2010cell function, revealing that Th cells and neurons can be regulated by similar signals in tissue\u2010specific responses.<\/jats:p>","DOI":"10.1002\/eji.201344422","type":"journal-article","created":{"date-parts":[[2014,8,29]],"date-time":"2014-08-29T00:49:02Z","timestamp":1409273342000},"page":"3605-3613","source":"Crossref","is-referenced-by-count":12,"title":["The neurotrophic factor receptor RET regulates IL\u201010 production by in vitro polarised T helper 2 cells"],"prefix":"10.1002","volume":"44","author":[{"given":"Afonso R. 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