Chinh Tran1, Creed M Stary2, Jan M Schilling1, Brandon Bentley1, Hemal H Patel1, David M Roth3. 1. Department of Anesthesiology, Veterans Affairs San Diego Healthcare System, University of California, San Diego, La Jolla, CA, United States. 2. Department of Anesthesia, Stanford University, Stanford, CA, United States. 3. Department of Anesthesiology, Veterans Affairs San Diego Healthcare System, University of California, San Diego, La Jolla, CA, United States. Electronic address: droth@ucsd.edu.
Abstract
AIMS: Caveolins are structural proteins clustered in lipid-rich regions of plasma membrane involved in coordinating signal transduction in various organ systems. While caveolin-1 (Cav-1) has been shown to regulate lymphocyte activation, the role of caveolin-3 (Cav-3) in immune system signaling has not been investigated. We tested the hypothesis that Cav-3 modulates lymphocyte activation. MAIN METHODS: Lymphocyte/leukocyte subpopulations from WT and Cav-3 mice were profiled with flow cytometry. Cytokine production in quiescent and activated splenocytes from WT and Cav-3 mice was assessed with ELISA. KEY FINDINGS: Levels of T-cells, monocytes, and natural killer cells were not different between WT and KO mice, however KO mice had lower B-cell population-percentage. Functionally, activated lymphocytes from Cav-3 KO mice demonstrated significantly reduced expression of IL-2 compared to WT, while expression of TNFα, IL-6, and IL-10 was not different. Finally, expression of IL-17 was significantly reduced in T-helper cells from KO mice, while IFNγ was not, suggesting that Cav-3 is a determinant in the development of the Th-17 subpopulation. SIGNIFICANCE: This study is the first to demonstrate that Cav-3 may be a novel participant in B-cell expression, T-cell cytokine production and activation of inflammation.
AIMS: Caveolins are structural proteins clustered in lipid-rich regions of plasma membrane involved in coordinating signal transduction in various organ systems. While caveolin-1 (Cav-1) has been shown to regulate lymphocyte activation, the role of caveolin-3 (Cav-3) in immune system signaling has not been investigated. We tested the hypothesis that Cav-3 modulates lymphocyte activation. MAIN METHODS: Lymphocyte/leukocyte subpopulations from WT and Cav-3mice were profiled with flow cytometry. Cytokine production in quiescent and activated splenocytes from WT and Cav-3mice was assessed with ELISA. KEY FINDINGS: Levels of T-cells, monocytes, and natural killer cells were not different between WT and KO mice, however KO mice had lower B-cell population-percentage. Functionally, activated lymphocytes from Cav-3 KO mice demonstrated significantly reduced expression of IL-2 compared to WT, while expression of TNFα, IL-6, and IL-10 was not different. Finally, expression of IL-17 was significantly reduced in T-helper cells from KO mice, while IFNγ was not, suggesting that Cav-3 is a determinant in the development of the Th-17 subpopulation. SIGNIFICANCE: This study is the first to demonstrate that Cav-3 may be a novel participant in B-cell expression, T-cell cytokine production and activation of inflammation.
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