Researchers of a study of tonsillar tissue from patients with IgA nephropathy (IgAN) found a higher proportion of plasmacytoid dendritic cells (pDCs) than in patients with chronic tonsillitis. In IgAN samples, greater pDC abundance was associated with higher expression of Toll-like receptor 9 (TLR9), B cell activating factor, and a proliferation-inducing ligand (APRIL). The ratio of galactose-deficient IgA1 (Gd-IgA1) to total IgA correlated with both pDC frequency and APRIL expression. When purified pDCs were added back to tonsillar cells from patients with IgAN, Gd-IgA1 production increased. This supports a possible role for mucosal pDCs in the earliest stages of IgAN pathogenesis.
The findings add to evidence that mucosal immune dysregulation may contribute to the production of pathogenic IgA in IgAN. Animal experiments also showed that depleting pDCs reduced aberrantly glycosylated IgA after TLR9 stimulation, suggesting that pDCs may influence this process through TLR9 signaling and possibly APRIL. However, the study was small, relied on tonsillar tissue, and did not establish a direct causal role for the TLR9-APRIL pathway. Further research is needed to determine whether selectively targeting mucosal pDC activity or downstream signaling could translate into future therapeutic strategies.
Reference: Fukao Y, Suzuki H, Nihei Y, et al. Plasmacytoid dendritic cells modulate the production of mucosal IgA in IgA nephropathy. Nephrol Dial Transplant. 2026 Apr 30;41(5):888-897. doi: 10.1093/ndt/gfaf216.
