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

作者：Toyama Masahiko; Kudo Daisuke; Aoyagi Tetsuji; Miyasaka Tomomitsu; Ishii Keiko; Kanno Emi; Kaku Mitsuo; Kushimoto Shigeki; Kawakami Kazuyoshi^*

来源：Microbiology and Immunology, 2018, 62(2): 111-123.

DOI：10.1111/1348-0421.12564

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

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 -galactosylceramide (-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 -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 -GalCer/LPS-treated mice. Treatment with anti-IFN- mAb enhanced the expression of SLC and the accumulation of Treg cells in the lungs of -GalCer/LPS-treated mice, whereas giving recombinant (r)IFN- reduced the number of Treg cells in mice treated with LPS alone. IL-10 production was significantly lower in -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-1, IL-6, TNF-, and IFN-) and chemokines (including MCP-1, RANTES, IP-10, Mig, MIP-2, and KC) in -GalCer/LPS-treated mice. Treatment with anti-IFN- mAb enhanced IL-10 production in -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.

• 出版日期2018-2