Researchers utilizing single-cell RNA sequencing and spatial transcriptomics disclosed immune cell subsets implicated in the clinical variability of systemic sclerosis. Specific monocyte and CD8+ T cell populations correlate with organ involvement such as scleroderma renal crisis and interstitial lung disease, respectively. This fine-resolution immune profiling provides novel biomarkers and mechanistic insights to guide personalized treatment strategies for this complex autoimmune condition.