TY - JOUR
T1 - Congenital Deficiency of Conventional Dendritic Cells Promotes the Development of Atopic Dermatitis-Like Inflammation
AU - Nishikawa, Yotaro
AU - Fukaya, Tomohiro
AU - Fukui, Takehito
AU - Uto, Tomofumi
AU - Takagi, Hideaki
AU - Nasu, Junta
AU - Miyanaga, Noriaki
AU - Riethmacher, Dieter
AU - Choijookhuu, Narantsog
AU - Hishikawa, Yoshitaka
AU - Amano, Masahiro
AU - Sato, Katsuaki
N1 - Funding Information:
We thank all members of the animal facility at University of Miyazaki; Yumiko Sato and Rumi Sunachi for secretarial assistance.
Publisher Copyright:
© Copyright © 2021 Nishikawa, Fukaya, Fukui, Uto, Takagi, Nasu, Miyanaga, Riethmacher, Choijookhuu, Hishikawa, Amano and Sato.
PY - 2021/7/27
Y1 - 2021/7/27
N2 - 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.
AB - 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.
KW - atopic dermatitis
KW - dendritic cells
KW - homeostatic feedback loop
KW - immune homeostasis
KW - type 2 immune responses
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U2 - 10.3389/fimmu.2021.712676
DO - 10.3389/fimmu.2021.712676
M3 - Article
C2 - 34394115
AN - SCOPUS:85112446919
SN - 1664-3224
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 712676
ER -