Abstract
Atopic dermatitis (AD) is a common pruritic inflammatory skin disease characterized by impaired epidermal barrier function and dysregulation of Thelper-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. Here, we describe the impact of the constitutive loss of cDCs on the progression of AD-like inflammation by using binary transgenic (Tg) mice that constitutively lacked CD11chi cDCs. 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 Staphylococcus aureus (S. aureus), that associated with disease flare. Thus, cDCs maintains immune homeostasis to prevent the occurrence of immune abnormalities to maintain the functional skin barrier for mitigating AD flare.
Highlights
Dendritic cells (DCs) are important professional antigen (Ag)presenting cells (APCs) that play pleiotropic roles in integration and fine-tuning of the immune system, bridging between innate and adaptive immunity [1,2,3]
R-DT a chain (DTA) mice and CD11c-Cre mice, which had been backcrossed for ten generations on to C57BL/6 mice, were cross-mated for generating CD11c-Cre:R-DTA mice used as DCD11chi conventional dendritic cells (cDCs) mice, and their WT littermates were used as CD11chi cDCsufficient control mice
Cre:R-DTA mice revealed almost complete elimination of CD11chi cDCs in Spl and ear-draining lymph nodes (EDLNs) in the homeostatic conditions when compared with WT mice (Figures S1C, D, S2A in Supplementary Materials)
Summary
Dendritic cells (DCs) are important professional antigen (Ag)presenting cells (APCs) that play pleiotropic roles in integration and fine-tuning of the immune system, bridging between innate and adaptive immunity [1,2,3]. The pathophysiology of AD is complex and results from impaired epidermal barrier function and cutaneous inflammation as well as a type 2 helper T (TH2)-skewed immune dysregulation with elevated serum immunoglobulin (Ig)E level and peripheral blood eosinophilia, caused by the interaction between genetic and environmental predispositions [10,11,12,13,14,15]. While the lineage of DCs have been considered to play decisive roles in the pathogenesis of cutaneous allergic diseases [19,20,21,22,23,24,25,26,27,28,29], the intrinsic role of cDCs in the maintenance of skin immune homeostasis in the steady-state conditions that impacts the onset of eczematous inflammation remains unclear
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
