NDLI: Blockade of phosphatidylinositol 3-kinase PI3KÎ´ or PI3KÎ³ reduces IL-17 and ameliorates imiquimod-induced psoriasis-like dermatitis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Perino, Alessia Soro, Elisabetta Okkenhaug, Klaus Dapavo, Paolo Hirsch, Emilio Ji, Hong Roller, Anne
Description	Country affiliation: Switzerland Author Affiliation: Roller A ( Rheumatology Research, Merck Serono S.A., 1211 Geneva, Switzerland.)
Abstract	Psoriasis is a chronic inflammatory skin disease triggered by interplay between immune mediators from both innate and adaptive immune systems and skin tissue, in which the IL-23/IL-17 axis is critical. PI3KÎ´ and PI3KÎ³ play important roles in various immune cell functions. We found that mice lacking functional PI3KÎ´ or PI3KÎ³ are largely protected from imiquimod (IMQ)-induced psoriasis-like dermatitis, correlating with reduced IL-17 levels in the lesions, serum, and the draining lymph nodes. TCRÎ³Î´ T cells were the major IL-17-producing population in the draining lymph nodes and were significantly diminished in IMQ-treated PI3KÎ´ knockin and PI3KÎ³ knockout mice. We also show that PI3KÎ´ and PI3KÎ³ inhibitors reduced IFN-Î³ production by human TCRÎ³Î´ T cells and IL-17 and IFN-Î³ production by PBMCs from psoriatic or healthy donors. In addition, inhibition of PI3KÎ³, but not PI3KÎ´, blocked chemotaxis of CCR6(+)IL-17-producing cells from IMQ-treated mice or healthy human donors. Taken together, these data indicate that PI3KÎ´ and/or PI3KÎ³ inhibitors should be considered for treating IL-17-driven diseases, such as psoriasis.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	9
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Aminoquinolines Toxicity Class Ib Phosphatidylinositol 3-kinase Antagonists & Inhibitors Dermatitis Immunology Therapy Interleukin-17 Phosphatidylinositol 3-kinases Psoriasis Animals Genetics Physiology Pathology Disease Models, Animal Gene Knock-in Techniques Biosynthesis Blood Lymph Nodes Metabolism Mice Mice, Inbred C57bl Mice, Knockout Chemically Induced T-lymphocyte Subsets Enzymology Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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