Biomolecules (Mar 2024)

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
https://doi.org/10.3390/biom14030360
Journal volume & issue
Vol. 14, no. 3
p. 360

Abstract

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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.

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