Background <p>Interstitial lung disease (ILD) is the most frequent complication of systemic sclerosis (SSc), associated with a poor prognosis and limited treatments. T helper 2 (Th2) cells play a key role in SSc pathogenesis, with T cell inducible co-stimulator (ICOS) involved in Th2 differentiation and IL-4 expression. However, the specific role of ICOS⁺ Th2 cells in SSc-ILD remains unclear.</p> Methods <p>Peripheral blood mononuclear cells (PBMCs) from SSc patients and healthy controls were analyzed via mass cytometry (CyTOF). The CD4⁺CXCR5⁻ICOS⁺IL-4⁺ T cell subset was further characterized using flow cytometry. In vitro, human lung fibroblasts were co-cultured with differentiated CD4⁺ICOS⁺IL-4⁺ cells, and fibrotic gene expression was measured. An in vivo SSc-ILD model was induced via bleomycin instillation, and the frequency of CD4⁺CXCR5⁻ICOS⁺IL-4⁺ cells was assessed in the lung. Functional contributions were evaluated by transferring CD4⁺ICOS⁺IL-4⁺ cells into Rag2^−/− mice, followed by histological analysis of lung inflammation and fibrosis.</p> Results <p>CyTOF identified a CD4⁺CCR4⁺ICOS⁺ T cell subset significantly increased in SSc-ILD patients, defined as ICOS⁺ Th2 cells by the absence of CXCR5, CXCR3, and CCR6 and the presence of CCR4. Elevated CD4⁺CXCR5⁻ICOS⁺IL-4⁺ T cells were confirmed in SSc-ILD patient PBMCs and in the lungs of bleomycin-treated mice. Functionally, ICOS⁺ Th2 cells induced high expression of <i>Vimentin</i>, <i>Fibronectin</i>, and <i>α-SMA</i> in fibroblasts when co-cultured with TGF-β. Adoptive transfer of ICOS⁺ Th2 cells into Rag2^−/− mice caused lung inflammation and upregulated fibrosis-related genes, including <i>α-SMA</i>, <i>Col1a1</i>, <i>Col1a2</i>, and <i>Col3a1</i>.</p> Conclusion <p>This study identifies ICOS⁺ Th2 cells as a key subset contributing to SSc-ILD inflammation and fibrosis, highlighting their potential as therapeutic targets.</p>