Mast cell-derived IL-13 downregulates IL-12 production by skin dendritic cells to inhibit the TH1 cell response to cutaneous antigen exposure

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:147

Article

Leyva-Castillo, Juan Manuel¹  Das, Mrinmoy¹  Artru, Emilie¹  Yoon, Juhan^1,2  Galand, Claire^1,3  Geha, Raif S.¹ 

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

[2] MirimGENE Co Ltd, Yeonsugu, South Korea

[3] Agenus Inc, Lexington, MA USA

关键词: Atopic dermatitis;    IL-13;    dendritic cells;    T(H)1 cells;   

DOI  :  10.1016/j.jaci.2020.11.036

来源: Elsevier

【 摘 要 】

Background: Atopic dermatitis (AD) is characterized by a skin barrier defect aggravated by mechanical injury inflicted by scratching, a T(H)2 cell-dominated immune response, and susceptibility to viral skin infections that are normally restrained by a T(H)1 cell response. The signals leading to a T(H)2 cell-dominated immune response in AD are not completely understood. Objective: Our aim was to determine the role of IL-13 in initiation of the T-H cell response to cutaneously encountered antigens. Methods: Wild-type, Il13(-/-), Il1rl1(-/-), and Il4ra(-/-) mice, as well as mice with selective deficiency of IL-13 in mast cells (MCs) were studied; in addition, dendritic cells (DCs) purified from the draining lymph nodes of tape-stripped and ovalbumin (OVA)-sensitized skin were examined for their ability to polarize naive OVA-TCR transgenic CD4(+) T cells. Cytokine expression was examined by reverse-transcriptase quantitative PCR, intracellular flow cytometry, and ELISA. Contact hypersensitivity to dinitrofluorobenzene was examined. Results: Tape stripping caused IL-33-driven upregulation of Il13 expression by skin MCs. MC-derived IL-13 acted on DCs from draining lymph nodes of OVA-sensitized skin to selectively suppress their ability to polarize naive OVA-TCR transgenic CD4(+) T cells into IFN-gamma-secreting cells. MC-derived IL-13 inhibited the T(H)1 cell response in contact hypersensitivity to dinitrofluorobenzene. IL-13 suppressed IL-12 production by mouse skin-derived DCs in vitro and in vivo. Scratching upregulated IL13 expression in human skin, and IL-13 suppressed the capacity of LPS-stimulated human skin DCs to express IL-12 and promote IFN-gamma secretion by CD4(+) T cells. Conclusion: Release of IL-13 by cutaneous MCs in response to mechanical skin injury inhibits the T(H)1 cell response to cutaneous antigen exposure in AD.

【 授权许可】

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