1. Congenital Deficiency of Conventional Dendritic Cells Promotes the Development of Atopic Dermatitis-Like Inflammation.
- Author
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Nishikawa Y, Fukaya T, Fukui T, Uto T, Takagi H, Nasu J, Miyanaga N, Riethmacher D, Choijookhuu N, Hishikawa Y, Amano M, and Sato K
- Subjects
- Adaptive Immunity, Animals, CD11 Antigens analysis, Calcitriol analogs & derivatives, Calcitriol therapeutic use, Cell Count, Cytokines immunology, Dendritic Cells chemistry, Dendritic Cells immunology, Dermatitis, Atopic immunology, Dermatitis, Atopic pathology, Dermatologic Agents therapeutic use, Disease Progression, Disease Susceptibility, Eczema immunology, Eczema pathology, Feedback, Physiological, Homeostasis immunology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Specific Pathogen-Free Organisms, Staphylococcal Skin Infections etiology, Staphylococcus aureus pathogenicity, Th2 Cells immunology, Dendritic Cells pathology, Dermatitis, Atopic congenital
- Abstract
Atopic dermatitis (AD) is a common pruritic inflammatory skin disease characterized by impaired epidermal barrier function and dysregulation of Thelper-2 (T
H 2)-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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nishikawa, Fukaya, Fukui, Uto, Takagi, Nasu, Miyanaga, Riethmacher, Choijookhuu, Hishikawa, Amano and Sato.)- Published
- 2021
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