TY - JOUR
T1 - Priming Microenvironments Dictate Cytokine Requirements for T Helper 17 Cell Lineage Commitment
AU - Hu, Wei
AU - Troutman, Ty Dale
AU - Edukulla, Ramakrishna
AU - Pasare, Chandrashekhar
N1 - Funding Information:
We thank J. Forman, R. Medzhitov, S. Rath, A. Unni, and C. Wuelfing for helpful comments on the manuscript. This work was supported by National Institutes of Health grant AI082265 to C.P.
PY - 2011/12/23
Y1 - 2011/12/23
N2 - 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 differentiation are guided by DCs residing in various tissues. These results reveal fundamental differences by which the systemic, mucosal, and cutaneous immune systems guide Th17 cell lineage commitment.
AB - 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 differentiation are guided by DCs residing in various tissues. These results reveal fundamental differences by which the systemic, mucosal, and cutaneous immune systems guide Th17 cell lineage commitment.
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U2 - 10.1016/j.immuni.2011.10.013
DO - 10.1016/j.immuni.2011.10.013
M3 - Article
C2 - 22137454
AN - SCOPUS:84355162720
SN - 1074-7613
VL - 35
SP - 1010
EP - 1022
JO - Immunity
JF - Immunity
IS - 6
ER -