Dectin-2 promotes house dust mite-skewed Th2 response through the activation of cDC2s

Yulan Qu; Xiaotian Ma; Jiewen Deng; Yan Shang; Kun Shang; Xinyu Wang; Zhenhong Guo; Chong Bai

doi:10.1016/j.cellimm.2022.104558

Dectin-2 promotes house dust mite-skewed Th2 response through the activation of cDC2s

Cell Immunol. 2022 Aug:378:104558. doi: 10.1016/j.cellimm.2022.104558. Epub 2022 Jun 6.

Authors

Yulan Qu¹, Xiaotian Ma², Jiewen Deng³, Yan Shang⁴, Kun Shang², Xinyu Wang², Zhenhong Guo⁵, Chong Bai⁶

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Shanghai Changhai Hospital, the First Affiliated Hospital of Second Military Medical University, 200433 Shanghai, People's Republic of China.
² National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, 200433 Shanghai, People's Republic of China.
³ Department of Cardiology Disease, the Second Affiliated Hospital of Zhejiang University, Zhejiang University, 310009 Zhejiang, People's Republic of China.
⁴ Department of Respiratory and Critical Care Medicine, Shanghai Changhai Hospital, the First Affiliated Hospital of Second Military Medical University, 200433 Shanghai, People's Republic of China; Department of General Practice, Shanghai Changhai Hospital, the First Affiliated Hospital of Second Military Medical University, 200433 Shanghai, People's Republic of China.
⁵ National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, 200433 Shanghai, People's Republic of China. Electronic address: guozh@immunol.org.
⁶ Department of Respiratory and Critical Care Medicine, Shanghai Changhai Hospital, the First Affiliated Hospital of Second Military Medical University, 200433 Shanghai, People's Republic of China. Electronic address: bc7878@sohu.com.

PMID: 35717749
DOI: 10.1016/j.cellimm.2022.104558

Abstract

The role of Dectin-2 (gene symbol, Clec4n) in house dust mite (HDM) induced Th2 immune response and the exact mechanism remains controversial. In this study, we illustrated that, Clec4n^-/- mice had decreased Th2 immune response following HDM challenge, which may ascribe to dramatically reduced type 2 conventional dendritic cells (cDC2s) in lung of Clec4n^-/- mice, as cDC2s from lung of Clec4n^-/- mice after challenging had less ability to induce Th2 response with decreased production of IL-4/IL-13. Further in vitro experiments showed the activation of Clec4n^-/--BMDCs significantly decreased after HDM stimulation accompanied with decreased activation of Syk-NF-κB and Syk-JNK signal pathway. Importantly, Dectin-2 expression in PBMCs from asthmatic patients was significantly higher than that in healthy controls. Taken together, these results demonstrated that Dectin-2 could promote cDC2s activation in lung, which polarizes Th2 immune response outlining a novel mechanism of asthma development.

Keywords: Asthma; Dectin-2; Syk-JNK; Th2 immune response; cDC2s.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Asthma*
Cytokines / metabolism
Dendritic Cells
Dermatophagoides pteronyssinus
Disease Models, Animal
Lectins, C-Type
Lung
Mice
Mice, Knockout
Pyroglyphidae*
Th2 Cells

Substances

Cytokines
Lectins, C-Type
dectin-2, mouse