Signaling the Way Home

Science's STKE  06 Mar 2007:
Vol. 2007, Issue 376, pp. tw73
DOI: 10.1126/stke.3762007tw73

T cells "home" to extralymphoid tissues that correspond to the regions in which they were initially activated; for instance, effector T cells initially activated in gut-associated lymphoid tissue home to the gut, whereas T cells activated in lymph nodes associated with the skin return to the skin. This preferential migration depends on the induction by dendritic cells (DCs) of receptors on T cells that recognize ligands found in distinct regions (see Mebius). Sigmundsdottir et al. found that exposure to the active form of vitamin D3 [1,25(OH)2D3] stimulated the expression of the CC chemokine receptor 10 (CCR10) on T cells activated in vitro, allowing them to migrate toward the CCR10 ligand CCL27 (a chemokine secreted by epidermal keratinocytes). The expression of receptors involved in homing to the gut, however, was inhibited. Induction of CCR10 expression by 1,25(OH)2D3 depended on interleukin-12 in naïve T cells but not in those activated before 1,25(OH)2D3 exposure. Microarray analysis revealed that monocyte-derived DCs expressed the enzymes required to process inactive vitamin D3 (cholecalciferol, which is produced in skin exposed to sunlight) into 1,25(OH)2D3; moreover, T cell-DC cocultures, monocyte-derived DCs, and DCs isolated from lymph vessels draining skin all converted inactive vitamin D3 to 1,25(OH)2D3. When T cells were activated by cocultured DCs, cholecalciferol stimulated expression of CCR10; it was ineffective during activation by antibodies directed against CD3 and CD28. Thus, the authors propose that DCs process epidermally derived vitamin D3 into a form that can be used to direct T cell homing to skin.

H. Sigmundsdottir, J. Pan, G. F. Debes, C. Alt, A. Habtezion, D. Soler, E. C. Butcher, DCs metabolize sunlight-induced vitamin D3 to "program" T cell attraction to the epidermal chemokine CCL27. Nat. Immunol. 8, 285-293 (2007). [PubMed]

R. E. Mebius, Vitamins in control of lymphocyte migration. Nat. Immunol. 8, 229-230 (2007). [PubMed]