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Recovery from acute lung injury can be regulated via modulation of regulatory T cells and Th17 cells
Author(s) -
Wang Linlin,
Wang Xiaocen,
Tong Lin,
Wang Jian,
Dou Maosen,
Ji Shimeng,
Bi Jing,
Chen Cuicui,
Yang Dong,
He Hong,
Bai Chunxue,
Zhou Jian,
Song Yuanlin
Publication year - 2018
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12715
Subject(s) - foxp3 , bronchoalveolar lavage , inflammation , immunology , lung , antibody , lipopolysaccharide , rar related orphan receptor gamma , chemistry , medicine , microbiology and biotechnology , biology , immune system
Acute lung injury ( ALI ) is a severe inflammatory disease, for which no specific treatment exists. The decreased ratio of regulatory T cells ( CD 4 + CD 25 + FoxP3 Tregs) and Th17 cells is implicated in ALI and inflammation. We here investigated whether maintaining the balance of CD 4 + CD 25 + Foxp3 + Tregs and Th17 cells can alleviate lung injury. For CD 4 + CD 25 + FoxP3 Treg depletion, 200 μg of an anti‐ CD 25 antibody was administered intraperitoneally per mouse on days −3 and −1 before lipopolysaccharide ( LPS ) instillation. And 150 μg of TGF ‐β was administered intraperitoneally per mouse on day 0 after LPS instillation. To down‐regulate of Th17 cells, 200 μg per mouse of isotype, IL ‐17 or IL ‐22 antibodies were injected intraperitoneally into mice at days 0 after LPS instillation. We detected lung morphology; lung wet‐to‐dry weight ratio; protein concentration, the count of total cells, neutrophils and macrophages, and cytokines in bronchoalveolar lavage fluid ( BALF ). And we also evaluated the percentage of CD 4 + CD 25 + Foxp3 + Tregs in lung, and Th17 cells in lung. CD 4 + CD 25 + Foxp3 + Tregs depletion via anti‐ CD 25 treatment or TGF ‐β neutralization delayed recovery of ALI . The prolonged inflammation was mainly dominated by neutrophils, macrophages and Th17 cells. Furthermore, inhibition of Th17 cells via monoclonal antibodies against IL ‐17 and IL ‐22 alleviated ALI inflammation by inhibiting the recruitment of neutrophils and macrophages, increasing the number of CD 4 + CD 25 + Foxp3 + Tregs. Our findings support a critical role for CD 4 + CD 25 + Foxp3 + Tregs in regulating from ALI pathophysiology, and a potential therapeutic role for the inhibition of Th17 cells in ALI treatment. These findings provide a rationale for treating patients with ALI by modulating CD 4 + CD 25 + Foxp3 + Tregs and Th17 cells.