Phthalate ester‐induced thymic stromal lymphopoietin mediates allergic dermatitis in mice

Immunology - Tập 128 Số 1pt2 - 2009
Tomomi Shigeno1, Mayako Katakuse1, Tomoyuki Fujita2, Yohei Mukoyama2, Hideki Watanabe1
1these authors contributed equally to this work
2Drug Discovery Research, Kyoto R&D Centre, Maruho Co., Ltd, Chudoji, Kyoto, Japan.

Tóm tắt

SummaryRecently air pollutants and irritants have been labelled as possible exogenous risk factors for allergic disorders. Although the underlying causes of allergic disorders such as atopic dermatitis and asthma remain unclear, the T helper type 2 (Th2) cell‐mediated allergic inflammatory cascade may contribute to their pathogenesis. In the last decade, it has been documented that one of the candidates for triggering Th2 commitment is thymic stromal lymphopoietin (TSLP), the expression of which is up‐regulated in the lesions of allergic patients. Here, we describe TSLP function in a fluorescein isothiocyanate (FITC) ‐induced contact hypersensitivity (CHS) model. A cytokine profile indicated that the model was dominantly mediated by the Th2 milieu. Interestingly, TSLP was increased in the skin during the sensitization phase when stimulated by a solvent, dibutyl phthalate (DBP), but not by FITC hapten or another solvent, acetone. Ear swelling in FITC‐induced CHS was totally abrogated by removing DBP from the sensitization or elicitation phase, and was restored by complementary injection of TSLP. Inversely, the ear swelling was suppressed by injection of small interfering RNA against TSLP during the sensitization phase, which was concomitant with decreasing expression of interleukin‐4 at the swollen skin site. Taken together, DBP‐induced TSLP during the sensitization phase plays a role in establishing FITC‐induced CHS and may be one of the causes of Th2 commitment in the model, suggesting that certain environmental toxins, such as DBP, may endow pro‐allergic and atopic predisposition in humans or animals.

Từ khóa


Tài liệu tham khảo

10.1111/1523-1747.ep12325538

10.4049/jimmunol.159.5.2484

10.1046/j.1523-1747.1998.00239.x

Kitagaki H, 1999, Distinct in vivo and in vitro cytokine profiles of draining lymph node cells in acute and chronic phases of contact hypersensitivity: importance of a type 2 cytokine‐rich cutaneous milieu for the development of an early‐type response in the chronic phase, J Immunol, 163, 1265, 10.4049/jimmunol.163.3.1265

10.1038/ni805

10.1084/jem.20051135

10.1016/S0165-2427(02)00066-1

10.4049/jimmunol.174.12.8183

10.1084/jem.20041503

10.1111/j.1600-0668.2006.00468.x

10.1111/j.1365-2222.2006.02574.x

10.1159/000106422

10.1093/intimm/dxh073

10.1111/j.1348-0421.2007.tb03914.x

Tang A, 1996, Suppression of murine allergic contact dermatitis by CTLA4Ig. Tolerance induction of Th2 responses requires additional blockade of CD40‐ligand, J Immunol, 157, 117, 10.4049/jimmunol.157.1.117

10.1016/j.it.2007.04.007

Dhaya S, 2007, In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation, J Clin Invest, 117, 3868, 10.1172/JCI33559

10.1046/j.1365-2567.1997.00360.x

Rui H, 2008, TSLP acts on infiltrating effector T cells to drive allergic skin inflammation, Proc Natl Acad Sci USA, 105, 11875, 10.1073/pnas.0801532105

10.1111/j.1600-0536.2007.01220.x

Loureiro G, 2005, Urban versus rural environment – any differences in aeroallergens sensitization in an allergic population of Cova da Beira, Portugal?, Eur Ann Allergy Clin Immunol, 37, 187

10.1016/S0190-9622(94)70213-6

Oie L, 1997, Residential exposure to plasticizers and its possible role in the pathogenesis of asthma, Environ Health Perspect, 105, 972, 10.1289/ehp.97105972

10.1289/ehp.10498

10.1289/ehp.8985

Thông tin
Thông tin xuất bản

Immunology

Tập 128 Số 1pt2

Thông tin tác giả