CD69 Signaling in Eosinophils Induces IL-10 Production and Apoptosis via the Erk1/2 and JNK Pathways, Respectively

Dan Van Bui; Linh Manh Nguyen; Akira Kanda; Hanh Hong Chu; Nhi Kieu Thi Le; Yasutaka Yun; Yoshiki Kobayashi; Kensuke Suzuki; Akitoshi Mitani; Akihiro Shimamura; Kenta Fukui; Shunsuke Sawada; David Dombrowicz; Hiroshi Iwai

doi:10.3390/biom14030360

CD69 Signaling in Eosinophils Induces IL-10 Production and Apoptosis via the Erk1/2 and JNK Pathways, Respectively

Biomolecules. 2024 Mar 18;14(3):360. doi: 10.3390/biom14030360.

Authors

Dan Van Bui^{1

2

3}, Linh Manh Nguyen¹, Akira Kanda^{1

4

5}, Hanh Hong Chu^{1

6}, Nhi Kieu Thi Le¹, Yasutaka Yun¹, Yoshiki Kobayashi^{1

5}, Kensuke Suzuki¹, Akitoshi Mitani¹, Akihiro Shimamura¹, Kenta Fukui¹, Shunsuke Sawada⁷, David Dombrowicz⁸, Hiroshi Iwai¹

Affiliations

¹ Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, Osaka 573-1010, Japan.
² Allergy and Clinical Immunology Department, Hanoi Medical University, Hanoi 115000, Vietnam.
³ Allergy, Immunology and Dermatology Department, E Hospital, Hanoi 122000, Vietnam.
⁴ Laboratory Medicine Center, Kansai Medical University Hospital, Osaka 573-1010, Japan.
⁵ Allergy Center, Kansai Medical University Hospital, Osaka 573-1010, Japan.
⁶ Allergy, Immunology and Rheumatology Department, National Children Hospital, Hanoi 115000, Vietnam.
⁷ Dentistry and Oral Surgery and Care Center, Kansai Medical University Hospital, Osaka 573-1010, Japan.
⁸ University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, 59000 Lille, France.

Abstract

Introduction: Eosinophils contribute to the pathogenesis of allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis. We previously reported that human tissue eosinophils have high CD69 expression compared to blood eosinophils, and its expression is correlated with disease severity and the number of infiltrated eosinophils. However, biological CD69 signaling activity in eosinophils remains unclear.

Methods: CD69 expression on lung tissue eosinophils obtained from mice with ovalbumin-induced asthma was measured using flow cytometry. CD69 crosslinking was performed on eosinophils purified from the spleen of IL-5 transgenic mice to investigate CD69 signaling and its function in eosinophils. Then, qPCR, Western blot, enzyme-linked immunosorbent assay, and survival assay results were analyzed.

Results: Surface CD69 expression on lung tissue eosinophils in the asthma mice model was 2.91% ± 0.76%, whereas no expression was detected in the healthy group. CD69-expressed eosinophils intrinsically have an upregulation of IL-10 mRNA expression. Moreover, CD69 crosslinking induced further pronounced IL-10 production and apoptosis; these responses were mediated via the Erk1/2 and JNK pathways, respectively.

Conclusions: Our results suggested that CD69⁺ eosinophils play an immunoregulator role in type 2 inflammation, whereas activated tissue eosinophils contribute to the pathogenesis of asthma.

Keywords: CD69; Erk1/2; IL-10; JNK; asthma; crosslinking; eosinophil; survival; type 2 inflammation.

MeSH terms

Animals
Antigens, CD / metabolism
Apoptosis
Asthma* / metabolism
Eosinophils* / metabolism
Humans
Interleukin-10 / genetics
Interleukin-10 / metabolism
MAP Kinase Signaling System
Mice

Substances

Antigens, CD
Interleukin-10
IL10 protein, mouse

Grants and funding

This work was supported by funding from the Academic Society for Research in Otolaryngology, Kansai Medical University (KMU); a research grant from the KMU research consortium; Ministry of Education, Culture, Sports, Science, and Technology (MEXT)–Supported Program for the Strategic Research Foundation at Private Universities (S1201038); and JSPS KAKENHI (JP 22K09717) Grant-in-Aid for Scientific Research (C). The branding program is a world-leading research university on intractable immune and allergic diseases. DD is supported by grants from the Agence Nationale de la Recherche (ANR) and the European Union: EGID ANR-10-LABX-46 and ANR-20-CE15-0026, Fondation pour la Recherche Médicale (FRM), Nouveaux Défis en Allergologie. All these funding institutions were not involved in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.