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Publication : Phosphatase Regulator NIPP1 Restrains Chemokine-Driven Skin Inflammation.

First Author  Verbinnen I Year  2020
Journal  J Invest Dermatol Volume  140
Issue  8 Pages  1576-1588
PubMed ID  31972250 Mgi Jnum  J:305104
Mgi Id  MGI:6690779 Doi  10.1016/j.jid.2020.01.008
Citation  Verbinnen I, et al. (2020) Phosphatase Regulator NIPP1 Restrains Chemokine-Driven Skin Inflammation. J Invest Dermatol 140(8):1576-1588
abstractText  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.
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