Tissue-specific induction of CCR6 and Nrp1 during early CD4+ T cell differentiation

Abstract

Upon differentiation, T cells acquire tissue-specific homing properties allowing efficient targeting of effector T cells into distinct inflamed organs. Priming of T cells within skin-draining, peripheral lymph nodes (pLNs) leads to the expression of E- and P-selectin ligands, which facilitate migration into inflamed skin, whereas activation within gut-draining, mesenteric LNs (mLNs) results in induction of chemokine receptor CCR9 and integrin α 4 β 7 , both required for migration of effector T cells into mucosal tissues. In addition to the local tissue microenvironment, both organ-specific dendritic cells and LN-resident stromal cells are critical factors to shape T cell migration properties. Here, we identify two additional homing-related molecules, CCR6 and Neuropilin-1 (Nrp1), upregulated in T cells early during differentiation solely in pLNs, but not mLNs. Surprisingly, intestinal inflammation resulted in an ameliorated induction of CCR6 and Nrp1 in pLNs, suggesting that a local inflammation within the gut can systemically alter T cell differentiation. Finally, transplantation of mLNs to a skin-draining environment revealed that LN stromal cells also contribute to efficient CCR6 induction in pLNs. Collectively, these findings identify further aspects of early T cell differentiation within skin-draining pLNs, which could be utilized to further develop tailored and highly specialized vaccination strategies.