Fas Signaling in Dendritic Cells Mediates Th2 Polarization in HDM-Induced Allergic Pulmonary Inflammation

Miaomiao Han; Miaomiao Han; Miaomiao Han; Ran Hu; Jingyu Ma; Baohua Zhang; Ce Chen; Huabin Li; Jun Yang; Gonghua Huang; Gonghua Huang

doi:10.3389/fimmu.2018.03045

Frontiers in Immunology (Dec 2018)

Fas Signaling in Dendritic Cells Mediates Th2 Polarization in HDM-Induced Allergic Pulmonary Inflammation

Miaomiao Han,
Miaomiao Han,
Miaomiao Han,
Ran Hu,
Jingyu Ma,
Baohua Zhang,
Ce Chen,
Huabin Li,
Jun Yang,
Gonghua Huang,
Gonghua Huang

Affiliations

Miaomiao Han: Department of Otolaryngology-Head and Neck Surgery, Center for Allergic and Inflammatory Diseases, Affiliated Eye and ENT Hospital, Fudan University, Shanghai, China
Miaomiao Han: Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Miaomiao Han: Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Ran Hu: Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Jingyu Ma: Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Baohua Zhang: Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Ce Chen: Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, China
Huabin Li: Department of Otolaryngology-Head and Neck Surgery, Center for Allergic and Inflammatory Diseases, Affiliated Eye and ENT Hospital, Fudan University, Shanghai, China
Jun Yang: Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Gonghua Huang: Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Gonghua Huang: Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, China

DOI: https://doi.org/10.3389/fimmu.2018.03045
Journal volume & issue: Vol. 9

Abstract

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Fas–Fas ligand (FasL) signaling plays an important role in the development of allergic inflammation, but the cellular and molecular mechanisms are still not well known. By using the bone marrow-derived dendritic cell (BMDC) transfer-induced pulmonary inflammation model, we found that house dust mite (HDM)-stimulated FAS-deficient BMDCs induced higher Th2-mediated allergic inflammation, associated with increased mucus production and eosinophilic inflammation. Moreover, FAS-deficient BMDCs promoted Th2 cell differentiation upon HDM stimulation in vitro. Compared to wild-type BMDCs, the Fas-deficient BMDCs had increased ERK activity and decreased IL-12 production upon HDM stimulation. Inhibition of ERK activity could largely increase IL-12 production, consequently restored the increased Th2 cytokine expression of OT-II CD4+ T cells activated by Fas-deficient BMDCs. Thus, our results uncover an important role of DC-specific Fas signaling in Th2 differentiation and allergic inflammation, and modulation of Fas signaling in DCs may offer a useful strategy for the treatment of allergic inflammatory diseases.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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