C-type lectin Mincle initiates IL-17-mediated inflammation in acute exacerbations of idiopathic pulmonary fibrosis

Abstract

RationaleAcute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has a poor prognosis and high mortality. However, there is limited information regarding the mechanisms of AE-IPF. AimsWe aimed to explore the function of macrophage-inducible C-type lectin (Mincle) in AE-IPF. MethodsIn the present study, Mincle was detected in the lung tissues of AE-IPF patients. Mincle-deficient (Mincle-/-) mice and wild-type C57BL/6 mice were administered bleomycin (BLM), followed by HSV1 viral infection to establish the AE-IPF model. ResultsMincle was increased in the lung tissues of AE-IPF patients compared with those with stable IPF (P = 0.04) and healthy controls (P = 0.009). The survival rate of the Mincle-/-+BLM+HSV group was higher than that of the WT+BLM+HSV group. The mice in the Mincle-/-+BLM+HSV group exhibited milder inflammation and lower acute lung injury scores (P = 0.008). Mincle was expressed on inflammatory monocytes and neutrophils (CD11b+Gr1 +F4/80-) and monocyte-derived macrophages (Mo-AMs, CD11b+Gr1 +F4/80 +) in the BALF of AE-IPF mice. Mo-AMs were significantly increased in the WT+BLM+HSV group compared with the WT+BLM+PBS (P < 0.0001) and Mincle-/-+BLM+HSV (P = 0.0009) groups. Deletion of Mincle decreased the proportion of Th17 cells and Mo-AMs in the Mincle-/-+BLM+HSV group. ConclusionsMincle contributed to acute inflammation in AE-IPF by promoting Th17 differentiation.