IL-12 instructs skin homing of human Th2 cells.
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Biedermann, Tilo, Lametschwandtner, Guenther, Tangemann, Kirsten, Kund, Juliana, Hinteregger, Sonja, Carballido-Perrig, Nicole, Rot, Antal, Schwaerzler, Christoph and Carballido, Jose (2006) IL-12 instructs skin homing of human Th2 cells. Journal of Immunology (Baltimore, Md. : 1950), 177 (6). pp. 3763-3770. ISSN 0022-1767
Abstract
Distinct pattern of homing receptors determines the tissue preference for T cells to exert their effector functions. This homing competence is mostly determined early during T cell activation of naive T cells. In contrast, mechanisms governing the acquisition of particular homing receptors by T cells of the memory phenotype remain enigmatic. Th2 cell-mediated allergic diseases tend to flare during infections despite that these infections prime APCs to produce the prototypic Th1 cell-differentiating cytokine IL-12. In this study, we investigate the effect of IL-12 on the regulation of cutaneous lymphocyte Ag (CLA) on differentiated Th2 cells and consequences of this expression for allergic inflammation. Upon activation with IL-12, CLA- Th2 cells rapidly up-regulated IL-12Rbeta2 chain, alpha(1-3)-fucosyltransferase VII, and CLA molecules. IL-12-mediated CLA expression on Th2 cells was functional because it mediated rolling of these Th2 cells on E-selectin in vitro and migration into human skin grafts in SCID mice. CLA induction occurred immediately after exposure to IL-12 and was independent of IFN-gamma expression. In accordance, the transcription factor mediating IFN-gamma expression, T-bet, does not directly affect CLA expression. However, CLA expression was further enhanced after IL-12 treatment of T-bet+ -transfected Th2 cells in agreement with an increased IL-12 responsiveness of these cells caused by T-bet. The finding that IL-12 conferred skin-homing potential to already differentiated Th2 cells before inducing a switch in their cytokine production profile may explain the observed exacerbation of allergic skin diseases following bacterial infections.
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| Date Deposited: | 14 Dec 2009 13:57 |
| Last Modified: | 31 Jan 2013 01:12 |
| URI: | https://oak.novartis.com/id/eprint/603 |