In this study, we hypothesized that calpain activation promotes macrophage polarization toward M1 phenotype by relating the PI3K/AKT signaling, leading to ILD in bleomycin model of SSc, and that myeloid cell-specific Capns1-ko prevents macrophage polarization toward M1 phenotype thereby reducing bleomycin model of SSc-related ILD in mice. This evidence concerns the gene KRT8 and systemic sclerosis.