Eosinophil recruitment is dynamically regulated by interplay among lung dendritic cell subsets after allergen challenge

Shuying Yi,Xiuli Jing,Meixiang Wang,Rui Niu,Jianguo Liu,Jing Zhai,Guangming Zhu,Hua Tang,Yaping Wang,Yufang Shi,Hua Huang,Wengang Song,Li Kang

doi:10.1038/s41467-018-06316-9

Abstract

Eosinophil infiltration, a hallmark of allergic asthma, is essential for type 2 immune responses. How the initial eosinophil recruitment is regulated by lung dendritic cell (DC) subsets during the memory stage after allergen challenge is unclear. Here, we show that the initial eosinophil infiltration is dependent on lung cDC1s, which require nitric oxide (NO) produced by inducible NO synthase from lung CD24−CD11b+ DC2s for inducing CCL17 and CCL22 to attract eosinophils. During late phase responses after allergen challenge, lung CD24+ cDC2s inhibit eosinophil recruitment through secretion of TGF-β1, which impairs the expression of CCL17 and CCL22. Our data suggest that different lung antigen-presenting cells modulate lung cDC1-mediated eosinophil recruitment dynamically, through secreting distinct soluble factors during the memory stage of chronic asthma after allergen challenge in the mouse.

Highlights

Eosinophil infiltration, a hallmark of allergic asthma, is essential for type 2 immune responses
We show that in a chronic allergic asthma mouse model focused on the memory stage after allergen challenge, the initial eosinophil recruitment is mediated by cDC1s, which directly attract eosinophils by secreting CCL17 and CCL22
Our results showed that dendritic cell (DC) are capable of directly attracting eosinophils, and they are essential for the initial eosinophil accumulation after allergen challenge

Summary

Introduction

Eosinophil infiltration, a hallmark of allergic asthma, is essential for type 2 immune responses. How the initial eosinophil recruitment is regulated by lung dendritic cell (DC) subsets during the memory stage after allergen challenge is unclear. During late phase responses after allergen challenge, lung CD24+ cDC2s inhibit eosinophil recruitment through secretion of TGF-β1, which impairs the expression of CCL17 and CCL22. Our data suggest that different lung antigen-presenting cells modulate lung cDC1-mediated eosinophil recruitment dynamically, through secreting distinct soluble factors during the memory stage of chronic asthma after allergen challenge in the mouse. Correspondence and requests for materials should be addressed to Allergic inflammatory asthma is a common disease that affects people worldwide[1,2] It is mediated by several varieties of immune cells. It remains necessary to determine whether lung cDC1s are or are not essential for eosinophil recruitment after allergen challenge

Methods

Results

Conclusion