TY - JOUR
T1 - CCL27 is a crucial regulator of immune homeostasis of the skin and mucosal tissues
AU - Davila, Micha L.
AU - Xu, Ming
AU - Huang, Chengyu
AU - Gaddes, Erin R.
AU - Winter, Levi
AU - Cantorna, Margherita T.
AU - Wang, Yong
AU - Xiong, Na
N1 - Funding Information:
Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Numbers R01AR070887 and AR064831 (to N.X) and R01AR073364 (to Y.W.). The content is solely the responsibility of the authors and does not necessarily represent official views of the funding agencies. We thank Veronika Weaver for assistance. We thank the University of Texas Health Science Center of San Antonio Histology and Immunohistochemistry core facility and the Flow Cytometry Core Facility, the Pennsylvania State University Huck Institutes of the Life Sciences Flow Cytometry Facility, and the Microscopy Facility and Albert Einstein College of Medicine Gene Modification Facility for service and technical support. M.L.D. designed and performed the experiments, analyzed the data, and wrote the manuscript. M.X. C.H. E.H.S. E.G. and L.J. performed the experiments. Y.W. and M.T.C. provided critical reagents. N.X. designed the experiments, analyzed the data, wrote the manuscript, and supervised the study. Na Xiong has an US patent (# 10,588,941) that is related to this work. All the other authors declare no competing interests.
Funding Information:
Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Numbers R01AR070887 and AR064831 (to N.X) and R01AR073364 (to Y.W.). The content is solely the responsibility of the authors and does not necessarily represent official views of the funding agencies. We thank Veronika Weaver for assistance. We thank the University of Texas Health Science Center of San Antonio Histology and Immunohistochemistry core facility and the Flow Cytometry Core Facility, the Pennsylvania State University Huck Institutes of the Life Sciences Flow Cytometry Facility, and the Microscopy Facility and Albert Einstein College of Medicine Gene Modification Facility for service and technical support.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/6/17
Y1 - 2022/6/17
N2 - Abundant immune cells reside in barrier tissues. Understanding the regulation of these cells can yield insights on their roles in tissue homeostasis and inflammation. Here, we report that the chemokine CCL27 is critical for establishment of resident lymphocytes and immune homeostasis in barrier tissues. CCL27 expression is associated with normal skin and hair follicle development independent of commensal bacterial stimulation, indicative of a homeostatic role for the chemokine. Accordingly, in the skin of CCL27-knockout mice, there is a reduced presence and dysregulated localization of T cells that express CCR10, the cognate receptor to CCL27. Besides, CCL27-knockout mice have overreactive skin inflammatory responses in an imiquimod-induced model of psoriasis. Beyond the skin, CCL27-knockout mice have increased infiltration of CCR10+ T cells into lungs and reproductive tracts, the latter of which also exhibit spontaneous inflammation. Our findings demonstrate that CCL27 is critical for immune homeostasis across barrier tissues.
AB - Abundant immune cells reside in barrier tissues. Understanding the regulation of these cells can yield insights on their roles in tissue homeostasis and inflammation. Here, we report that the chemokine CCL27 is critical for establishment of resident lymphocytes and immune homeostasis in barrier tissues. CCL27 expression is associated with normal skin and hair follicle development independent of commensal bacterial stimulation, indicative of a homeostatic role for the chemokine. Accordingly, in the skin of CCL27-knockout mice, there is a reduced presence and dysregulated localization of T cells that express CCR10, the cognate receptor to CCL27. Besides, CCL27-knockout mice have overreactive skin inflammatory responses in an imiquimod-induced model of psoriasis. Beyond the skin, CCL27-knockout mice have increased infiltration of CCR10+ T cells into lungs and reproductive tracts, the latter of which also exhibit spontaneous inflammation. Our findings demonstrate that CCL27 is critical for immune homeostasis across barrier tissues.
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U2 - 10.1016/j.isci.2022.104426
DO - 10.1016/j.isci.2022.104426
M3 - Article
C2 - 35663027
AN - SCOPUS:85131065165
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 6
M1 - 104426
ER -