Role of IL-25 on Eosinophils in the Initiation of Th2 Responses in Allergic Asthma

Bo Peng; Lin Sun; Meng Zhang; Huacheng Yan; Guochao Shi; Zhenwei Xia; Ranran Dai; Wei Tang

doi:10.3389/fimmu.2022.842500

Role of IL-25 on Eosinophils in the Initiation of Th2 Responses in Allergic Asthma

Front Immunol. 2022 May 9:13:842500. doi: 10.3389/fimmu.2022.842500. eCollection 2022.

Authors

Bo Peng^{1

2

3}, Lin Sun^{1

2

3}, Meng Zhang⁴, Huacheng Yan^{1

2

3}, Guochao Shi^{1

2

3}, Zhenwei Xia⁴, Ranran Dai^{1

2

3}, Wei Tang^{1

2

3}

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai, China.
⁴ Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Background: Eosinophils act as a secondary antigen-presenting cell (APC) to stimulate Th cell responses against antigens. IL-25 plays a significant role in eosinophil activation in allergic asthma. The role of IL-25 on the classic APC functions of dendritic cells has been elucidated. However, whether IL-25 facilitates eosinophils for antigen presentation is unknown.

Objective: To elucidate the role of IL-25 on eosinophils antigen presenting function during allergic asthma and its related mechanism.

Methods: Eosinophils from allergic asthma subjects were cultured with IL-25 and HDM to identify the co-stimulator molecules expression. Co-cultures of patient eosinophils and autologous naïve CD4⁺ T cells in the same culture system were to explore whether eosinophils had the capacity to promote Th cell differentiation in response to IL-25 engagement. In asthma mouse model, IL-25^-/- mice were exposed to HDM to investigate the effect of IL-25 on eosinophils during the sensitization phase. The impact of IL-25 on the capacity for eosinophils taking up antigens was evaluated. Mouse bone marrow derived eosinophils (BmEOS) were co-cultured with naïve CD4⁺T cells sorted from spleens under HDM and IL-25 stimulation to identify T cell differentiation.

Results: IL-25 upregulated HLA-DR, PD-L1, and OX-40L expression on eosinophils from allergic asthma patients. IL-25 and HDM co-sensitized eosinophils promoted Th2 differentiation. In mouse model, IL-25^-/- mice experienced restrained allergic pulmonary inflammation and reduced eosinophils recruitment and antigen uptake capacity during the early sensitization phase. In vitro, IL-25 promoted antigen uptake by eosinophils. In BmEOS and naïve CD4⁺T cells co-culture, IL-25 accreted the proportion of CD4⁺Th2 cells, which was absent in CD4⁺T cells culture alone.

Conclusion: Our data identify a novel role of IL-25 in enhancing eosinophils antigen uptake and co-stimulator molecules expression to induce Th2 priming in the context of allergic inflammation.

Keywords: APC; IL-25; Th2 response; allergic asthma; eosinophil.

Publication types

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

MeSH terms

Animals
Asthma*
Cytokines / metabolism
Eosinophils
Humans
Mice
Pulmonary Eosinophilia*
Th2 Cells

Substances

Cytokines