Roles of Clara cell 10-kD protein and type 2 innate lymphoid cells in allergic rhinitis

Cell Cycle. 2021 Sep;20(18):1923-1934. doi: 10.1080/15384101.2021.1966961. Epub 2021 Aug 26.

Abstract

This study examined the potential roles of CC10 (Clara cell 10-kD protein) and ILC2s (type 2 innate lymphoid cells) in allergic rhinitis (AR). After ovalbumin was used to construct the AR model, microarray analysis was performed to reveal the key differentially expressed genes. The phenotypic changes of nasal mucosa were examined by H&E staining. Western blot analysis, qRT-PCR, ELISA and immunohistochemistry were performed to identify the levels of cytokines. The lineage markers (CD127 and CD117) of ILC2s were detected using immunofluorescence. The microarray analysis and qRT-PCR results showed that CC10 overexpression inhibited the expression of A20, BAFF, and IL-4 R in vivo. Also, CC10 overexpression was found to ameliorate the damage of nasal mucosa in AR mice. Investigations revealed that the ILC2s were activated in AR mice and AR patients with high levels of IgE, IgG1, IL-4, IL-5, IL-13, IL-25, and IL-33. Moreover, CD127+ was found to activate ILC2s. However, CC10 overexpression suppressed the activation of ILC2s. In conclusion, this research suggested that CC10 could suppress the activation of ILC2s to attenuate the damage of nasal mucosa and that CD127+ may be a biomarker of the activation of ILC2s in AR mice and AR patients.

Keywords: AR; CC10; ILC2s; allergic rhinitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Female
  • HEK293 Cells
  • Humans
  • Immunity, Innate*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / genetics
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Nasal Mucosa / immunology
  • Nasal Mucosa / metabolism
  • Ovalbumin / adverse effects
  • Rhinitis, Allergic / chemically induced
  • Rhinitis, Allergic / immunology*
  • Rhinitis, Allergic / metabolism*
  • Signal Transduction / genetics*
  • Signal Transduction / immunology
  • Transfection
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • Uteroglobin / genetics
  • Uteroglobin / metabolism*

Substances

  • Biomarkers
  • Cytokines
  • SCGB1A1 protein, human
  • Scgb1a1 protein, mouse
  • Ovalbumin
  • Uteroglobin

Grants and funding

This work is supported by National Natural Science Foundation of China (81400448, 81800891, 81470677).