IL-4Rα signalling in B cells and T cells play differential roles in acute and chronic atopic dermatitis

被引：7

作者：

Scibiorek, Martyna ^{[1
,2
]}

Mthembu, Nontobeko ^{[1
]}

Mangali, Sandisiwe ^{[1
,2
]}

Ngomti, Amkele ^{[1
]}

Ikwegbue, Paul ^{[1
]}

Brombacher, Frank ^{[1
,2
,3
]}

Hadebe, Sabelo ^{[1
]}

机构：

[1] Univ Cape Town, Fac Hlth Sci, Dept Pathol, Div Immunol, Cape Town, South Africa

[2] Univ Cape Town, Inst Infect Dis & Mol Med IDM, Int Ctr Genet Engn & Biotechnol ICGEB, Hlth Sci Fac,Div Immunol, Cape Town, South Africa

[3] Univ Cape Town, Inst Infect Dis & Mol Med IDM, Fac Hlth Sci, Wellcome Ctr Infect Dis Res Afr CIDRI Africa, ZA-7925 Cape Town, South Africa

来源：

SCIENTIFIC REPORTS | 2023年 / 13卷 / 01期

基金：

新加坡国家研究基金会; 英国惠康基金; 英国医学研究理事会; 芬兰科学院;

关键词：

IL-4; RECEPTOR; MOUSE MODEL; ECZEMA; ASSOCIATION; MATURATION; RESPONSES; PROTEIN; ASTHMA; ADULTS; ALPHA;

D O I：

10.1038/s41598-022-26637-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Atopic dermatitis (AD) is a common pruritic inflammatory skin disease with complex environmental and genetic predisposing factors. Primary skin barrier dysfunction and aberrant T helper 2 (TH2) responses to common allergens, together with increased serum IgE antibodies, characterise the disease. B and T cells are essential in the disease manifestation, however, the exact mechanism of how these cells is involved is unclear. Targeting interleukin 4 receptor alpha (IL-4R alpha), an IL-4/IL-13 signalling axis, with dupilumab shows efficacy in AD. We investigated the importance of IL-4R alpha signalling specifically on B and T cells during acute and chronic models of AD. We used House dust mite (HDM) and Ovalbumin (OVA) in chronic models and a low-calcemic analog of vitamin D (MC903) for acute models of AD. We used mb1(cre)IL-4R alpha(-/lox), iLCK(cre)IL-4R alpha(-/lox), (LCKIL)-I-cre-4R alpha(-/lox), CD4(cre)IL-4R alpha(-/lox), Foxp3(cre)IL-4R alpha(-/lox) and IL-4R alpha(-/lox) littermate controls. IL-4R alpha-responsive B cells were essential in serum IgE levels, but not in epidermal thickening in both chronic and acute models. IL-4R alpha-responsive T cells were essential in epidermal thickening in the pan-T cell, but not CD4 or CD8 T cells suggesting the importance of gamma delta T cells during acute AD. Our results suggest that IL-4R alpha responsiveness on innate T cells regulates acute atopic dermatitis, while on B cells it regulates IgE.

引用

页数：11

共 58 条

[21] Requirement for IL-13 independently of IL-4 in experimental asthma [J].