Psoriasis is a chronic inflammatory
skin disease mediated by host immune responses. Plasmacytoid dendritic cells (pDC) and
interferon (IFN)-α secreted by pDC are involved in the initiation of
psoriasis.
Mannan-binding lectin (MBL), a vital component of the
complement pathway, plays a critical role in innate immune defense and the inflammatory response. Our previous study found that MBL could exacerbate skin
inflammation in psoriatic mice, but the effect of MBL on pDC remains unstudied. Herein, we revealed that the circulating level of MBL was elevated in patients with
psoriasis compared with the healthy controls. Moreover, the MBL level was positively correlated with disease severity, relative inflammatory
cytokine levels, and peripheral blood (PB) pDC frequency in
psoriasis. An in vitro study determined that the MBL
protein could promote the differentiation of human pDC and upregulate the production of relative inflammatory
cytokines and
chemokines. Additionally, MBL-deficient (MBL-/- ) mice exhibited decreased accumulation of pDC in lymph nodes, spleens, and skin lesions with reduced secretion of pDC-related
cytokines compared with wild-type (WT) mice in the preliminary stage of
psoriasis induced by
imiquimod. Notably, the differentiation of pDC from bone marrow (BM) cells derived from MBL-/- mice was weakened compared with that from WT mice upon
Fms-like tyrosine kinase 3 ligand (Flt3L) incubation. Mechanistic research indicated that the
signal transducer and activator of transcription 3 (STAT3)-interferon regulatory
factor 8 (IRF8) axis was responsible for MBL-modulated pDC differentiation. In summary, these results suggest that MBL exacerbates the severity of
psoriasis by enhancing pDC differentiation and pDC-related
cytokine secretion via the STAT3-IRF8 axis, thus providing a new target for
psoriasis treatment.