Human β-Defensin 3 and Its Mouse Ortholog Murine β-Defensin 14 Activate Langerhans Cells and Exacerbate Psoriasis-Like Skin Inflammation in Mice

Abstract

Our data show that one-third of patients with PD have autoantibodies to Col XVII that also bind to TH þ neurons. The lack of reactivity of PD autoantibodies with skin suggests the autoantibodies develop from neuronal Col XVII. The subset of patients with neurologic disease that develop BP likely result from epitope spreading to regions of Col XVII that are pathogenic in skin. A key question that remains is whether Col XVII autoantibodies have a detrimental effect on PD or are otherwise predictive of disease onset/outcomes. Finally, these data suggest loss of tolerance to neuronal Col XVII may contribute to the risk for pemphigoid.

Stat3 activation in epidermal keratinocytes induces Langerhans cell activation to form an essential circuit for psoriasis via IL-23 production

“…Although DCs and T cells are known to play important roles in the pathogenesis of psoriasis, the role of LCs in mouse models of psoriasis-like inflammation is controversial [22][23][24][25][26][27]. LCs were reported to function of a negative immunoregulatory role via IL-10 and programmed cell death ligand-1 during the initiation and progression of psoriasis [22].…”

“…In contrast, LCs were required for the development of IMQ-treated psoriasis like inflammation in langerin-DTR KI mice [24,25]. In addition, human β-defensin 3 (HBD3) sustained and amplified psoriasis inflammation and HBD3 drived the production of IL-23 by LCs in psoriasis, which contributed to the pathogenesis of psoriasis [26]. Therefore, to elucidate the role of LCs in the pathogenesis of psoriasis, we used K5.Stat3C:langerin DTR KI mice, in which LCs could be depleted.…”

“…The role of LCs play in the pathogenesis of psoriasis remains controversial, since previous studies have reported conflicting results [22][23][24][25][26][27]. In the present study, we investigated whether LCs were involved in the development of psoriasis-like lesion in K5.…”

Resident and monocyte-derived Langerhans cells are required for imiquimod-induced psoriasis-like dermatitis model

“…Interestingly, an in vitro study of the human skin found that human LCs efficiently induced IL-22-producing CD4 + T cells [41], which may support the finding in our study that LCs are involved in the induction of IL-22 from T cells. Furthermore, it has been recently reported that activation of LCs by human b-defensin 3 sustained and amplified an IMQ-induced inflammation in mice [42]. However, currently it is not clear how murine LCs specifically regulate gd low T cells to produce IL-17A and IL-22 upon IMQ application.…”

Dynamic Changes in Resident and Infiltrating Epidermal Dendritic Cells in Active and Resolved Psoriasis

“…In the dermis, inflammatory DCs accumulate and contribute to the inflammatory environment through the production of tumor necrosis factor (TNF), inducible nitric oxide synthase, IL-12 (Brunner et al, 2013;Guttman-Yassky et al, 2007;Hansel et al, 2011;Lowes et al, 2005;Zaba et al, 2009), and IL-23 (Cai et al, 2011;Lee et al, 2004;Teunissen et al, 2012;Tonel et al, 2010;Yawalkar et al, 2009). In lesional epidermis, LCs display impaired migrational capacity (Cumberbatch et al, 2006;Shaw et al, 2010); elevated expression of CXCL9, CXCL10, and CCL20 (Fujita et al, 2011); and increased IL-23 production in response to TLR3 stimulation (Sweeney et al, 2016). Compared with LCs, epidermal DCs (eDCs) in lesional psoriasis display similar or higher gene expression of chemokines (Fujita et al, 2011).…”