IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization

被引：76

作者：

Yoon, Juhan ^{[1
,2
,13
]}

Leyva-Castillo, Juan Manuel ^{[1
,2
]}

Wang, Guoxing ^{[3
]}

Galand, Claire ^{[1
,2
]}

Oyoshi, Michiko K. ^{[1
,2
]}

Kumar, Lalit ^{[1
,2
]}

Hoff, Sabine ^{[1
,2
,14
]}

He, Rui ^{[1
,2
,15
]}

Chervonsky, Alexander ^{[7
]}

Oppenheim, Joost J. ^{[8
]}

Kuchroo, Vijay K. ^{[5
]}

van den Brink, Marcel R. M. ^{[9
]}

Malefyt, Rene De Waal ^{[10
]}

Tessier, Philippe A. ^{[11
]}

Fuhlbrigge, Robert ^{[1
,2
]}

Rosenstiel, Philip ^{[12
]}

Terhorst, Cox ^{[3
]}

Murphy, George ^{[4
,6
]}

Geha, Raif S. ^{[1
,2
]}

机构：

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

[2] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA

[3] Harvard Med Sch, Div Immunol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

[4] Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA

[5] Harvard Med Sch, Ctr Neurol Dis, Brigham & Womens Hosp, Boston, MA 02115 USA

[6] Harvard Med Sch, Div Dermatopathol, Brigham & Womens Hosp, Boston, MA 02115 USA

[7] Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA

[8] NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA

[9] Mem Sloan Kettering Canc Ctr, Dept Immunol & Med, New York, NY 10065 USA

[10] Merck Res Labs, Palo Alto, CA 94304 USA

[11] Ctr Hosp Univ Laval, Ctr Rech, Ste Foy, PQ G1V 4G2, Canada

[12] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany

[13] Sungkyunkwan Univ, DRC, C&C Res Labs, 2066 Seobu Ro, Suwon 440746, Gyeonggi Do, South Korea

[14] Bayer Pharma AG, Dept Immunotherapy & Antibody Drug Conjugates, D-13353 Berlin, Germany

[15] Fudan Univ, Shanghai Med Coll, Dept Immunol, Shanghai 200030, Peoples R China

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2016年 / 213卷 / 10期

基金：

美国国家卫生研究院;

关键词：

INNATE LYMPHOID-CELLS; PATHOGENIC T(H)17 CELLS; ATOPIC-DERMATITIS; CUTTING EDGE; T-CELLS; IMMUNE-RESPONSES; EPITHELIAL-CELLS; INTERLEUKIN; 22; HOST-DEFENSE; INFLAMMATION;

D O I：

10.1084/jem.20150376

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Atopic dermatitis (AD) is a Th2-dominated inflammatory skin disease characterized by epidermal thickening. Serum levels of IL-22, a cytokine known to induce keratinocyte proliferation, are elevated in AD, and Th22 cells infiltrate AD skin lesions. We show that application of antigen to mouse skin subjected to tape stripping, a surrogate for scratching, induces an IL-22 response that drives epidermal hyperplasia and keratinocyte proliferation in a mouse model of skin inflammation that shares many features of AD. DC- derived IL-23 is known to act on CD4(+) T cells to induce IL-22 production. However, the mechanisms that drive IL-23 production by skin DCs in response to cutaneous sensitization are not well understood. We demonstrate that IL-23 released by keratinocytes in response to endogenous TLR4 ligands causes skin DCs, which selectively express IL-23R, to up-regulate their endogenous IL-23 production and drive an IL-22 response in naive CD4(+) T cells that mediates epidermal thickening. We also show that IL-23 is released in human skin after scratching and polarizes human skin DCs to drive an IL-22 response, supporting the utility of IL-23 and IL-22 blockade in AD.

引用

页码：2147 / 2166

页数：20

共 31 条

[31] Effect of TLR4 engagement on TLR3-induced proinflammatory signaling in dendritic cells through IL-10, STAT3, and p38-dependent pathways and on antimelanoma CD8+T-cell priming.
Bogunovic, D.
Manches, O.
Yewdall, A.
Marie, I.
Levy, D. E.
Bhardwaj, N.
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (15)

← 1 2 3 4 →