Figure 4.

Endothelial dysfunctions and immune alterations in anti-MDA5 dermatomyositis. In the skin, CXCL10, a keratinocyte and endothelial-derived chemokine, induces the recruitment of CD8⁺CXCR3⁺ T cells, potentially autoreactive and leading to keratinocytes death. Endothelin released by injured endothelial cells, is a strong vasoconstrictor which can induce local ischemia responsible for cutaneous ulcers. In the lung, CX3CL1 can be produced by vascular pulmonary endothelial cells following IFN-I exposure. CX3CL1 recruits CX3CR1⁺ alternative alveolar macrophages (M2). Alveolar M2 macrophages, as well as airway epithelial cells, release stromal cell-derived factor 1 (SDF-1) which induces the accumulation of intrapulmonary CD4⁺CXCR4⁺ T cells. CD4⁺CXCR4⁺ T cells produce profibrotic agents (transformation growth factor-β (TGF-β), α-smooth muscle actin (α-SMA) and collagen I), as well as IL-21, which promotes the differentiation of profibrotic CD8⁺ T cells. CD8⁺ T cells secrete IL-13, which stimulates macrophages to produce profibrotic factors.