Altered distribution, activation and increased IL-17 production of mucosal-associated invariant T cells in patients with acute respiratory distress syndrome

Abstract

ObjectiveMucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells that are engaged in a number of diseases, but their roles in acute respiratory distress syndrome (ARDS) are not fully examined yet. This study aimed to examine levels and functions of MAIT cells in patients with ARDS.MethodsPeripheral blood samples from patients with ARDS (n=50) and healthy controls (HCs, n=50) were collected. Levels of MAIT cells, cytokines, CD69, programmed cell death-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) were measured by flow cytometry.ResultsCirculating MAIT cell levels were significantly reduced in patients with ARDS than in HCs. MAIT cell levels were inversely correlated with disease severity and mortality. Cytokine production profiles in MAIT cells showed that percentages of interleukin (IL)-17 producing MAIT cell were significantly higher in patients with ARDS than in HCs. Patients with ARDS exhibited higher expression levels of CD69, PD-1 and LAG-3 in circulating MAIT cells. Moreover, levels of MAIT cells and expression levels of CD69, PD-1 and IL-17 in MAIT cells were higher in bronchoalveolar lavage fluid samples than in peripheral blood samples. Our in vitro experiments showed that MAIT cells triggered macrophages to produce proinflammatory cytokines such as tumour necrosis factor-α, IL-1β and IL-8.ConclusionsThis study demonstrates that circulating MAIT cells are numerically deficient in patients with ARDS. In addition, MAIT cells were found to be activated, migrate into lung, secrete IL-17 and then stimulate macrophages. These findings suggest that MAIT cells contribute to the worsening of inflammation in the lung of patients with ARDS.

Mucosal associated invariant T cells in ARDS: MAIT cells set fire to macrophages via cytokines

“…One possible explanation is recruitment of these cells from the blood into airways. The studies by Jouan and Kim clearly reveal that a decrease in circulating MAIT cells in patients with ARDS parallels their increase in airways, suggesting these cells contribute to the regulation of local inflammation 4 6…”

“…In this issue of Thorax, Kim and colleagues4 broaden our understanding of the pathological role of MAIT cells in acute respiratory distress syndrome (ARDS). ARDS is an acute respiratory illness featured by bilateral chest radiographical opacities with severe hypoxemia due to non-cardiogenic pulmonary oedema 56.…”

“…Although accumulating data implicate the clinical relevance of MAIT cells in ARDS, it is unclear how these findings can be incorporated into clinical practice. Kim and colleagues have suggested that activated MAIT cells migrate into the lung and potentiate macrophage activation via Th17-type cytokines 4. However, a previous study underscored that the production of Th1 cytokines in MAIT cells is also crucial for the activation of macrophages.…”