Congenital deficiency of conventional dendritic cells promotes atopic dermatitis-like inflammation in mice

Background: Atopic dermatitis (AD) is a common pruritic inflammatory skin disease characterized by impaired epidermal barrier function and dysregulation of T heper-2 (TH2)-biased immune responses. While the lineage of conventional dendritic cells (cDCs) are implicated to play decisive roles in T-cell immune responses, their requirement for the development of AD remains elusive. Therefore, we sought to determine the impact of the constitutive loss of cDCs on the progression of AD-like inflammation. Methods: CD11c-Cre:ROSA26-diphtheria toxin α chain (DTA) transgenic (Tg) mice that constitutively lacked CD11chi cDCs and wild-type (WT) littermates received topical application of a low calcemic analogue of vitamin D3 known as MC903 (calcipotriol) to compare the development of AD-like inflammation and immune responses as well as the colonization of Staphylococcus aureus (S. aureus) in eczematous skin. Results: Unexpectedly, the congenital deficiency of cDCs not only exacerbates the pathogenesis of AD-like inflammation but also elicits immune abnormalities with the increased composition and function of granulocytes and group 2 innate lymphoid cells (ILC2) as well as B cells possibly mediated through the breakdown of the Fms-related tyrosine kinase 3 ligand (Flt3L)-mediated homeostatic feedback loop. Furthermore, the constitutive loss of cDCs accelerates skin colonization of S. aureus, that associated with disease flare. Conclusion: cDCs maintains immune homeostasis to prevent the occurrence of immune abnormalities to maintain the functional skin barrier for mitigating AD flare.