|
KMID : 1225720220140060653
|
|
Allergy, Asthma & Immunology Research : AAIR
2022 Volume.14 No. 6 p.653 ~ p.673
|
|
|
Pulmonary IFN-γ Causes Lymphocytic Inflammation and Cough Hypersensitivity by Increasing the Number of IFN-γ-Secreting T Lymphocytes
|
|
Deng Zheng
Ding Wenbin
Li Fengying
Shen Shuirong
Huang Chuqin
Lai Kefang
|
|
|
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.
|
|
|
KEYWORD
|
|
|
Interferon-gamma, T lymphocytes, cough, CXC chemokine receptor 3
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
   
|