IL-21 R is essential for epicutaneous sensitization and allergic skin inflammation in humans and mice

被引：97

作者：

Jin, Haoli ^{[1
]}

Oyoshi, Michiko K. ^{[1
]}

Le, Yi ^{[2
,3
]}

Bianchi, Teresa ^{[4
]}

Koduru, Suresh ^{[1
]}

Mathias, Clinton B. ^{[1
]}

Kumar, Lalit ^{[1
]}

Le Bras, Severine ^{[1
]}

Young, Deborah ^{[5
]}

Collins, Mary ^{[5
]}

Grusby, Michael J. ^{[6
]}

Wenzel, Joerg ^{[7
]}

Bieber, Thomas ^{[7
]}

Boes, Marianne ^{[4
]}

Silberstein, Leslie E. ^{[2
,3
]}

Oettgen, Hans C. ^{[1
]}

Geha, Raif S. ^{[1
]}

机构：

[1] Childrens Hosp, Div Immunol, Boston, MA 02115 USA

[2] Childrens Hosp, Joint Program Transfus Med, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Boston, MA USA

[4] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA

[5] Wyeth Res, Cambridge, MA USA

[6] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA

[7] Univ Bonn, Dept Dermatol & Allergy, D-5300 Bonn, Germany

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2009年 / 119卷 / 01期

基金：

瑞士国家科学基金会;

关键词：

STEADY-STATE CONDITIONS; IFN-GAMMA PRODUCTION; T-CELL-ACTIVATION; ATOPIC-DERMATITIS; DENDRITIC CELLS; IN-VIVO; LANGERHANS CELLS; MURINE MODEL; MAST-CELLS; TH1; CELLS;

D O I：

10.1172/JCI32310

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Atopic dermatitis (AD) is a common allergic inflammatory skin disease caused by a combination of intense pruritus, scratching, and epicutaneous (e.c.) sensitization with allergens. To explore the roles of IL-21 and IL-21 receptor (IL-21R) in AD, we examined skin lesions from patients with AD and used a mouse model of allergic skin inflammation. IL-21 and IL-21R expression was upregulated in acute skin lesions of AD patients and in mouse skin subjected to tape stripping, a surrogate for scratching. The importance of this finding was highlighted by the fact that both rl21r(-/-) mice and WT mice treated with soluble IL-21R-IgG2aFc fusion protein failed to develop skin inflammation after e.c. sensitization of tape-stripped skin. Adoptively transferred OVA-specific WT CD4(+) T cells accumulated poorly in draining LNs (DLNs) of e.c. sensitized Il21r(-/-) mice. This was likely caused by both DC-intrinsic and nonintrinsic effects, because trafficking of skin DCs to DLNs was defective in Il21r(-/-) mice and, to a lesser extent, in WT mice reconstituted with Il21r(-/-) BM. More insight into this defect was provided by the observation that skin DCs from tape-stripped WT mice, but not Il21r(-/-) mice, upregulated CCR7 and migrated toward CCR7 ligands. Treatment of epidermal and dermal cells with IL-21 activated MMP2, which has been implicated in tracking of skin DCs. These results suggest an important role for IL-21R in the mobilization of skin DCs to DLNs and the subsequent allergic response to e.c. introduced antigen.

引用

页码：47 / 60

页数：14

共 60 条

[51] IL-21 inhibits IFN-γ production in developing Th1 cells through the repression of eomesodermin expression [J].