IL-12 instructs skin homing of human Th2 cells

Tilo Biedermann; Günther Lametschwandtner; Kirsten Tangemann; Julia Kund; Sonja Hinteregger; Nicole Carballido-Perrig; Antal Rot; Christoph Schwärzler; José M Carballido

IL-12 instructs skin homing of human Th2 cells

Tilo Biedermann, Günther Lametschwandtner, Kirsten Tangemann, Julia Kund, Sonja Hinteregger, Nicole Carballido-Perrig, Antal Rot, Christoph Schwärzler, José M Carballido

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	3763-70
Number of pages	8
Journal	Journal of Immunology
Volume	177
Issue number	6
Publication status	Published - 15 Sept 2006

Keywords

Adult
Animals
Antigens, Differentiation, T-Lymphocyte
Antigens, Neoplasm
Bacterial Infections
Cell Line
Cell Movement
Clone Cells
Dermatitis, Atopic
Fucosyltransferases
Humans
Interleukin-12
Membrane Glycoproteins
Mice
Mice, SCID
Receptors, Lymphocyte Homing
Skin
Skin Transplantation
Th2 Cells
Up-Regulation

Cite this

@article{44107b26bc1145aca1c2c25c27a92e27,

title = "IL-12 instructs skin homing of human Th2 cells",

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.",

keywords = "Adult, Animals, Antigens, Differentiation, T-Lymphocyte, Antigens, Neoplasm, Bacterial Infections, Cell Line, Cell Movement, Clone Cells, Dermatitis, Atopic, Fucosyltransferases, Humans, Interleukin-12, Membrane Glycoproteins, Mice, Mice, SCID, Receptors, Lymphocyte Homing, Skin, Skin Transplantation, Th2 Cells, Up-Regulation",

author = "Tilo Biedermann and G{\"u}nther Lametschwandtner and Kirsten Tangemann and Julia Kund and Sonja Hinteregger and Nicole Carballido-Perrig and Antal Rot and Christoph Schw{\"a}rzler and Carballido, {Jos{\'e} M}",

year = "2006",

month = sep,

day = "15",

language = "English",

volume = "177",

pages = "3763--70",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

number = "6",

}

TY - JOUR

T1 - IL-12 instructs skin homing of human Th2 cells

AU - Biedermann, Tilo

AU - Lametschwandtner, Günther

AU - Tangemann, Kirsten

AU - Kund, Julia

AU - Hinteregger, Sonja

AU - Carballido-Perrig, Nicole

AU - Rot, Antal

AU - Schwärzler, Christoph

AU - Carballido, José M

PY - 2006/9/15

Y1 - 2006/9/15

N2 - 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.

AB - 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.

KW - Adult

KW - Animals

KW - Antigens, Differentiation, T-Lymphocyte

KW - Antigens, Neoplasm

KW - Bacterial Infections

KW - Cell Line

KW - Cell Movement

KW - Clone Cells

KW - Dermatitis, Atopic

KW - Fucosyltransferases

KW - Humans

KW - Interleukin-12

KW - Membrane Glycoproteins

KW - Mice

KW - Mice, SCID

KW - Receptors, Lymphocyte Homing

KW - Skin

KW - Skin Transplantation

KW - Th2 Cells

KW - Up-Regulation

M3 - Article

C2 - 16951337

SN - 0022-1767

VL - 177

SP - 3763

EP - 3770

JO - Journal of Immunology

JF - Journal of Immunology

IS - 6

ER -