Background and aims In this observational cohort study, we assessed the prognostic value of DC-SIGN(+) cells in the pathogenesis and progression of IgA nephropathy (IgAN). Methods and results A total of 139 adult IgAN patients were enrolled into this study from June 2009 to June 2010. We characterised DC-SIGN(+) cells by immunohistochemistry or immunofluorescence in renal biopsy tissue. Correlations between the DC-SIGN, intercellular adhesion molecule 3 (ICAM-3), CD4 and CD8 were evaluated. Patients were classified into the DC-SIGN(high) and DC-SIGN(low) groups. Depending on an average of 100-month follow-up, the predictive value of DC-SIGN(+) cells in IgAN progression was analysed. DC-SIGN(+) cells were found frequently in IgAN kidneys while rarely observed in normal kidneys, and almost all DC-SIGN(+) cells expressed MHC-II. We also found that DC-SIGN(+) cells were adjacent to ICAM-3-positive CD4(+) and CD8(+) lymphocytes. The density of DC-SIGN(+) cells was positively and linearly correlated with the density of ICAM-3(+) cells, CD4(+) cells and CD8(+) cells in renal biopsy tissues. In the DC-SIGN(high) group, the degree of renal lesion and inflammatory cell infiltration was more severe compared to the DC-SIGN(low) group. Patients in the DC-SIGN(high) group also had increased incidences of deteriorating renal function during the follow up compared to patients in the DC-SIGN(low) group. Conclusions DC-SIGN(+) cells probably served as a potential contributor to exacerbate local inflammatory response. The density of DC-SIGN(+) cells was associated with the severity of renal lesions of the patients. High renal DC-SIGN(+) cell density might be used as a predictor of poor prognosis in patients with IgAN.