Livin promotes Th2-type immune response in airway allergic diseases

Immunol Res. 2022 Oct;70(5):624-632. doi: 10.1007/s12026-022-09294-9. Epub 2022 Jun 18.

Abstract

Objectives: To investigate the effects of livin on the Th2 immune response in airway allergic diseases (AAD) and explore the interaction among livin, GATA3, IL-4 in peripheral blood CD4+ T cells of AAD patients.

Methods: WT mice and livin KO mice were developed for model of AAD. Th2 cell levels in the lung tissues and spleen were assessed by flow cytometry. Also, it was assessed in the culture after exposing to livin inhibitor (Lp-15); the protein and mRNA levels of livin, GATA3 and IL-4 in peripheral blood CD4+ T cells isolated from patients with or without AAD were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. Finally, Co-immunoprecipitation (Co-IP) was employed to identify the interaction between livin and GATA3.

Results: Compared with WT mouse, Th2 cell frequency in lung tissues and spleen was significantly decreased in livin KO mouse; after adding Lp-15, the differentiation from Naive CD4+T cells in spleen to Th2 cells was blocked; the protein and mRNA levels of livin, GATA3 and IL-4 in AAD group were higher than that in control group. The levels of livin were positively correlated with IL-4, and GATA3 was also positively correlated with IL-4 and livin. GATA3 was detected in the protein complex co-precipitated with livin antibody, and livin was also detected in the protein complex co-precipitated by GATA3 antibody.

Conclusion: Livin increases the expression of IL-4 and facilitates naive CD4+ T cells to differentiate into Th2 cells, which triggers airway allergy.

Keywords: AAD; CD4+ T cells; GATA3; Livin; Th2 differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / immunology
  • Disease Models, Animal
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / immunology
  • Hypersensitivity
  • Immunity
  • Inhibitor of Apoptosis Proteins* / genetics
  • Inhibitor of Apoptosis Proteins* / immunology
  • Interleukin-4 / immunology
  • Mice
  • RNA, Messenger
  • Respiratory Hypersensitivity* / genetics
  • Respiratory Hypersensitivity* / immunology
  • Th2 Cells* / immunology

Substances

  • Cytokines
  • GATA3 Transcription Factor
  • Inhibitor of Apoptosis Proteins
  • RNA, Messenger
  • livin protein, mouse
  • Interleukin-4