Triggering Receptor Expressed on Myeloid Cells-2 Regulates Innate Lymphoid Cell Levels in Bleomycin-Induced Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis, a pathological change causing poor outcomes, is not reversible despite current antifibrotic therapy. Emerging evidence suggests that innate lymphoid cells (ILCs) mediate lung inflammation and fibrosis after stimulation by endogenous factors. Triggering receptor expressed on myeloid cells-2 (TREM2) is known to regulate inflammation in various diseases. However, the relationship between TREM2 and ILCs in pulmonary fibrosis is unclear. This study aimed to explore the role of TREM2 in regulating ILC activation in bleomycin (BLM)-induced pulmonary fibrosis. We first examined the role of TREM2 in regulating ILC expression in a mouse model of BLM-induced pulmonary fibrosis, and subsequently assessed the levels of ILCs, pulmonary fibrosis, and inflammation using histological staining and molecular biology techniques. These results were compared between wild-type (WT) and TREM2 knockout (KO) mice. Compared with those in WT mice, inflammatory cell aggregation and collagen fiber deposition were more prominent in TREM2-KO mice after intratracheal BLM injection. Compared with those in WT mice, there was a pronounced increase in GATA3 and RORγt expression in lung tissues from TREM2-KO mice. In adaptive transfer experiments, ILC-enriched population isolated from WT mice after BLM stimulation in vivo increased the expression of TGF-β, α-SMA, and collagen-1 in naïve WT mice. Immunofluorescence staining revealed GATA3 expression in the lung tissues of TREM2-KO mice after BLM stimulation. Compared with those receiving ILCs from WT mice, those receiving adoptive transfer of ILC-enriched population from TREM2-KO mice exhibited more lung injury and fibrosis. In conclusion, TREM2 decreases ILC activity to reduce BLM-induced pulmonary fibrosis.