Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. STKE, 6 March 2007
Vol. 2007, Issue 376, p. tw73
[DOI: 10.1126/stke.3762007tw73]

EDITORS' CHOICE

Immunology Signaling the Way Home

Elizabeth M. Adler

Science's STKE, AAAS, Washington, DC 20005, USA

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]

Citation: E. M. Adler, Signaling the Way Home. Sci. STKE 2007, tw73 (2007).



To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882