biostudies-literatureHu WNIAID NIH HHS1010-22https://www.ebi.ac.uk/biostudies/studies/S-EPMC3246047biostudies-literatureUnknown35(6)Activation of pattern recognition receptors on dendritic cells (DCs) and macrophages leads to secretion of cytokines that control differentiation of CD4(+) T cells. The current understanding is that interleukin-6 (IL-6) in combination with transforming growth factor-β (TGF-β) leads to generation of T helper 17 (Th17) lineage cells. Here, we have discovered that the cytokine requirements for Th17 cell polarization depend on the site of priming. Although IL-6 played a critical role in Th17 cell lineage priming in the skin and mucosal tissues, it was not required for Th17 cell priming in the spleen. In contrast, IL-1 played an irreplaceable role for priming of Th17 lineage cells in all tissues. Importantly, we have demonstrated that IL-6-independent and -dependent pathways of Th17 cell differImmunityPriming microenvironments dictate cytokine requirements for T helper 17 cell lineage commitment.PMC3246047R01 AI082265R01 AI082265-01A1AI082265Pasare CEdukulla RHu WTroutman TDfalsePriming microenvironments dictate cytokine requirements for T helper 17 cell lineage commitment.Activation of pattern recognition receptors on dendritic cells (DCs) and macrophages leads to secretion of cytokines that control differentiation of CD4(+) T cells. The current understanding is that interleukin-6 (IL-6) in combination with transforming growth factor-β (TGF-β) leads to generation of T helper 17 (Th17) lineage cells. Here, we have discovered that the cytokine requirements for Th17 cell polarization depend on the site of priming. Although IL-6 played a critical role in Th17 cell lineage priming in the skin and mucosal tissues, it was not required for Th17 cell priming in the spleen. In contrast, IL-1 played an irreplaceable role for priming of Th17 lineage cells in all tissues. Importantly, we have demonstrated that IL-6-independent and -dependent pathways of Th17 cell differ2011-01-01T00:00:00Z2011 Dec2025-04-22T04:56:25.04Z2019-03-27T00:47:22ZS-EPMC32460472213745410.1016/j.immuni.2011.10.013