The role and mechanism of regulatory T cells in indirect acute lung injury

Objective: To study the role and mechanism of CD(4)(+) CD(25)(+) FoxP3(+) regulatory T cells (Tregs) in the pathophysiological process of indirect acute lung injury (iALI) in mice. Methods: The iALI model was successfully induced by shock/cecal ligation and puncture method. Sham (n=8), cecal ligation and puncture (CLP, n=10), and hemorrhage (Hem, n=12) groups were established as controls. Two experimental groups were established: CLP+Hem (n=15) without Tregs adoptive transfer (AT), and CLP+Hem with Tregs adoptive transfer (CLP+Hem+AT, n=14). The number of Tregs, subsets of lymphocytes, neutrophil activity, apoptosis, cytokine levels and histopathological changes were measured in the lung tissue of each group. The protein exudation and the expression of IL-10 in bronchoalveolar lavage fluid (BALF) were also detected. After in vitro cell co-culture, the proliferation of activated T cells and the expression of IL-10, INF-γ and iNOS protein were detected. Results: The percentage and the absolute cell number of CD(4)(+) CD(25)(+) FoxP3(+) Tregs in lung tissue of iALI mice were (2.530±0.086)%, and (1.441±0.090)×10(4)/ml, respectively, which were significantly higher than the control groups (P<0.05). Adoptive transfer of Tregs could significantly decrease CD3-positive T lymphocytes, myeloperoxidase (MPO) activity, caspase-3 activity in lung tissue as well as protein leakage in BALF (P<0.05). Meanwhile interleukin-10 (IL-10) levels in lung tissue and BALF were up-regulated from (121.4±43.76) pg/ml to (201.0±61.96) pg/ml (t=2.776, P<0.05) and (206.2±90.88) pg/ml to (339.4±109.5) pg/ml (t=2.477, P<0.05), respectively. Histopathology was also significantly improved. The proliferation of activated T lymphocytes in the adoptive transfer Treg (AT-Treg) group (n=5) was significantly lower than that in the natural regulatory T cell (N-Treg) group (n=5, t=7.485, P<0.01) and the negative control group (n=5, t=16.66, P<0.01). However, iNOS enzyme inhibitor L-NMMA could significantly reduce the T cell proliferation (P<0.05). Conclusion: CD(4)(+)CD(25)(+)FoxP3(+) Tregs could reduce inflammatory reaction in mice with iALI, and the iNOS signaling pathway may be involved in this process.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:41

Enthalten in:

Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases - 41(2018), 12 vom: 12. Dez., Seite 959-966

Sprache:

Chinesisch

Beteiligte Personen:

Zhuang, W J [VerfasserIn]
Xie, Y [VerfasserIn]
Gu, J L [VerfasserIn]
Wei, S Y [VerfasserIn]

Links:

Volltext

Themen:

Animals
Cytokines
INOS
Interleukin-10
Journal Article
Respiratory distress syndrome, adult
T lymphocyte, regulatory

Anmerkungen:

Date Completed 11.02.2019

Date Revised 15.02.2019

published: Print

Citation Status MEDLINE

doi:

10.3760/cma.j.issn.1001-0939.2018.12.012

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM291525504