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Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2.
Fayngerts, Svetlana A; Wang, Zhaojun; Zamani, Ali; Sun, Honghong; Boggs, Amanda E; Porturas, Thomas P; Xie, Weidong; Lin, Mei; Cathopoulis, Terry; Goldsmith, Jason R; Vourekas, Anastassios; Chen, Youhai H.
Affiliation
  • Fayngerts SA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Wang Z; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Zamani A; Department of Immunology and Microbiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Sun H; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Boggs AE; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Porturas TP; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Xie W; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Lin M; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Cathopoulis T; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Goldsmith JR; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Vourekas A; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Chen YH; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Nat Immunol ; 18(12): 1353-1360, 2017 Dec.
Article in En | MEDLINE | ID: mdl-29058702
ABSTRACT
The polarization of leukocytes toward chemoattractants is essential for the directed migration (chemotaxis) of leukocytes. How leukocytes acquire polarity after encountering chemical gradients is not well understood. We found here that leukocyte polarity was generated by TIPE2 (TNFAIP8L2), a transfer protein for phosphoinositide second messengers. TIPE2 functioned as a local enhancer of phosphoinositide-dependent signaling and cytoskeleton remodeling, which promoted leading-edge formation. Conversely, TIPE2 acted as an inhibitor of the GTPase Rac, which promoted trailing-edge polarization. Consequently, TIPE2-deficient leukocytes were defective in polarization and chemotaxis, and TIPE2-deficient mice were resistant to leukocyte-mediated neural inflammation. Thus, the leukocyte polarizer is a dual-role phosphoinositide-transfer protein and represents a potential therapeutic target for the treatment of inflammatory diseases.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: T-Lymphocytes / Chemotaxis, Leukocyte / Intracellular Signaling Peptides and Proteins / Encephalomyelitis, Autoimmune, Experimental Limits: Animals Language: En Journal: Nat Immunol Year: 2017 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: T-Lymphocytes / Chemotaxis, Leukocyte / Intracellular Signaling Peptides and Proteins / Encephalomyelitis, Autoimmune, Experimental Limits: Animals Language: En Journal: Nat Immunol Year: 2017 Document type: Article