Pulmonary IFN-γ Causes Lymphocytic Inflammation and Cough Hypersensitivity by Increasing the Number of IFN-γ-Secreting T Lymphocytes.

Abstract

PURPOSE:

Respiratory viral infection increases the number of lung-resident T lymphocytes, which enhance cough sensitivity by producing interferon-γ (IFN-γ). It is poorly understood why IFN-γ-secreting T lymphocytes persist for a long time when the respiratory viruses have been removed.

METHODS:

Repeated pulmonary administration of IFN-γ and intraperitoneal injection with different inhibitors were used to study the effects of pulmonary IFN-γ in mice and guinea pigs.

RESULTS:

IFN-γ administration caused the increasing of IFN-γ-secreting T lymphocytes in both lung and blood, followed by the elevated physiological level of IFN-γ in the lung, the airway inflammation and the airway epithelial damage. IFN-γ administration also enhanced the cough sensitivity of guinea pigs. IFN-γ activated the STAT1 and extracellular signal-regulated kinase (ERK) pathways in lung tissues, released IFN-γ-inducible protein 10 (IP-10), and resulted in F-actin accumulation in lung-resident lymphocytes. The CXC chemokine receptor 3 (CXCR3) inhibitor potently suppressed all the IFN-γ-induced inflammatory changes. The STAT1 inhibitor mitigated IFN-γ-secreting T lymphocytes infiltration by inhibiting T lymphocytes proliferation. F-actin accumulation and the ERK1/2 pathway contributed to pulmonary IFN-γ-induced augmentation of the airway inflammation and increasing of IFN-γ-secreting T lymphocytes in blood.

CONCLUSIONS:

High physiological levels of IFN-γ in the lung may cause pulmonary lymphocytic inflammation and cough hypersensitivity by increasing the number of IFN-γ-secreting T lymphocytes through the IP-10 and CXCR3 pathways.

• Authors: Zheng Deng, Wenbin Ding, Fengying Li, Shuirong Shen, Chuqin Huang, Kefang Lai
• Journal: Allergy, asthma & immunology research (Allergy Asthma Immunol Res) Vol. 14 Issue 6 Pg. 653-673 (Nov 2022) ISSN: 2092-7355 [Print] Korea (South)
• PMID: 36426396 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.