The impact of Langerhans cells on Th17/Treg balance in psoriasis lesions.

Langerhans cells (LCs) play a crucial role in sensing and processing stimuli from the skin and the external environment. They are implicated in various skin disorders, acting either as pro-inflammatory agents or as regulatory elements. However, the exact function of LCs in the pathogenesis of psoriasis remains unclear. Psoriasis is characterized by a significant Th17/Treg immune imbalance. To elucidate the independent effect of Treg dysfunction on psoriatic inflammation, we established a Treg-inhibited psoriasis group using the Foxp3 inhibitor CMD178, in conjunction with LC depletion models to investigate the LC-Th17/Treg regulatory axis METHODS: Psoriasis models were established through the topical application of IMQ. Female C57BL/6 N mice were divided into three groups: control, IMQ-induced psoriasis, and Treg-depleted psoriasis. LCswere depleted using diphtheria toxin in Langerin-DTR mice, while Tregs were inhibited by CMD178. Inflammation was assessed through measurements of ear thickness, histopathology, apoptosis, and cytokine production. Additionally, RT-qPCR was utilized to detect the expression of S100A7, S100A8, and MMP2. Flow cytometry was employed to analyze the functional status of lymphocytes and T cell phenotypes. IMQ-induced psoriasis-like lesions exhibit activated LCs, an increase in Th17 cells, a decrease in Tregs, elevated levels of IL-17A and IL-22, and reduced levels of TGF-β and PD-L1. Depletion of LCs alleviated the lesions and restored the Th17/Treg balance, whereas depletion of Tregs exacerbated the inflammation. LCs play a central regulatory role in the psoriatic skin environment by influencing the Th17/Treg.