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Phosphatase Regulator NIPP1 Restrains Chemokine-Driven Skin Inflammation.
- Source :
-
The Journal of investigative dermatology [J Invest Dermatol] 2020 Aug; Vol. 140 (8), pp. 1576-1588. Date of Electronic Publication: 2020 Jan 21. - Publication Year :
- 2020
-
Abstract
- Nuclear inhibitor of protein phosphatase 1 (NIPP1) is a ubiquitously expressed nuclear protein that regulates functions of protein serine/threonine phosphatase-1 in cell proliferation and lineage specification. The role of NIPP1 in tissue homeostasis is not fully understood. This study shows that the selective deletion of NIPP1 in mouse epidermis resulted in epidermal hyperproliferation, a reduced adherence of basal keratinocytes, and a gradual decrease in the stemness of hair follicle stem cells, culminating in hair loss. This complex phenotype was associated with chronic sterile skin inflammation and could be partially rescued by dexamethasone treatment. NIPP1-deficient keratinocytes massively expressed proinflammatory chemokines and immunomodulatory proteins in a cell-autonomous manner. Chemokines subsequently induced the recruitment and activation of immune cells, in particular conventional dendritic cells and Langerhans cells, accounting for the chronic inflammation phenotype. The data identifies NIPP1 as a key regulator of epidermal homeostasis and as a potential target for the treatment of inflammatory skin diseases.<br /> (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Alopecia genetics
Alopecia pathology
Animals
Cell Adhesion immunology
Cell Proliferation genetics
Chemokines immunology
Dermatitis genetics
Dermatitis pathology
Disease Models, Animal
Epidermis immunology
Hair Follicle immunology
Hair Follicle pathology
Humans
Intracellular Signaling Peptides and Proteins genetics
Keratinocytes immunology
Keratinocytes pathology
Mice
Mice, Knockout
Alopecia immunology
Chemokines metabolism
Dermatitis immunology
Epidermis pathology
Intracellular Signaling Peptides and Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1747
- Volume :
- 140
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Journal of investigative dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 31972250
- Full Text :
- https://doi.org/10.1016/j.jid.2020.01.008