Attenuated accumulation of regulatory T cells and reduced production of interleukin 10 lead to the exacerbation of tissue injury in a mouse model of acute respiratory distress syndrome

Masahiko Toyama, Daisuke Kudo, Tetsuji Aoyagi, Tomomitsu Miyasaka, Keiko Ishii, Emi Kanno, Mitsuo Kaku, Shigeki Kushimoto, Kazuyoshi Kawakami

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Acute respiratory distress syndrome (ARDS) is a pathological condition that involves diffuse lung injury and severe hypoxemia caused by pulmonary and systemic diseases. We have established a mouse model of severe ARDS, developed by intratracheal injection of α-galactosylceramide (α-GalCer), an activator of natural killer T (NKT) cells, followed by LPS. In the present study, we used this model to investigate the regulatory mechanism in the early inflammatory response during acute lung injury. In α-GalCer/LPS-treated mice, the number of CD4+CD25+Foxp3+ regulatory T (Treg) cells and the expression of a Treg cell-tropic chemokine, secondary lymphoid-tissue chemokine (SLC), in the lungs was significantly lower than in mice treated with LPS alone. Giving recombinant (r)SLC increased the number of Treg cells in α-GalCer/LPS-treated mice. Treatment with anti-IFN-γ mAb enhanced the expression of SLC and the accumulation of Treg cells in the lungs of α-GalCer/LPS-treated mice, whereas giving recombinant (r)IFN-γ reduced the number of Treg cells in mice treated with LPS alone. IL-10 production was significantly lower in α-GalCer/LPS-treated mice than in mice treated with LPS alone. Giving rIL-10 prolonged survival and attenuated lung injury as a result of reduced production of inflammatory cytokines (such as IL-1β, IL-6, TNF-α, and IFN-γ) and chemokines (including MCP-1, RANTES, IP-10, Mig, MIP-2, and KC) in α-GalCer/LPS-treated mice. Treatment with anti-IFN-γ mAb enhanced IL-10 production in α-GalCer/LPS-treated mice. These results suggest that the attenuated accumulation of Treg cells may be involved in the development of severe ARDS through a reduction in the synthesis of IL-10.

Original languageEnglish
Pages (from-to)111-123
Number of pages13
JournalMICROBIOLOGY and IMMUNOLOGY
Volume62
Issue number2
DOIs
Publication statusPublished - 2018 Feb 1

Keywords

  • IL-10
  • NKT cell
  • acute lung injury
  • regulatory T cell

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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