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The kinase PKCα selectively upregulates interleukin-17A during Th17 cell immune responses.
- Source :
-
Immunity [Immunity] 2013 Jan 24; Vol. 38 (1), pp. 41-52. Date of Electronic Publication: 2013 Jan 03. - Publication Year :
- 2013
-
Abstract
- Transforming growth-factor β (TGFβ) has been implicated in T helper 17 (Th17) cell biology and in triggering expression of interleukin-17A (IL-17A), which is a key Th17 cell cytokine. Deregulated TGFβ receptor (TGFβR) signaling has been implicated in Th17-cell-mediated autoimmune pathogenesis. Nevertheless, the full molecular mechanisms involved in the activation of the TGFβR pathway in driving IL-17A expression remain unknown. Here, we identified protein kinase C α (PKCα) as a signaling intermediate specific to the Th17 cell subset in the activation of TGFβRI. We have shown that PKCα physically interacts and functionally cooperates with TGFβRI to promote robust SMAD2-3 activation. Furthermore, PKCα-deficient (Prkca(-/-)) cells demonstrated a defect in SMAD-dependent IL-2 suppression, as well as decreased STAT3 DNA binding within the Il17a promoter. Consistently, Prkca(-/-) cells failed to mount appropriate IL-17A, but not IL-17F, responses in vitro and were resistant to induction of Th17-cell-dependent experimental autoimmune encephalomyelitis in vivo.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Encephalomyelitis, Autoimmune, Experimental chemically induced
Encephalomyelitis, Autoimmune, Experimental genetics
Encephalomyelitis, Autoimmune, Experimental immunology
Gene Expression Regulation
Interleukin-17 immunology
Mice
Mice, Knockout
Myelin-Oligodendrocyte Glycoprotein adverse effects
Peptide Fragments adverse effects
Protein Kinase C-alpha genetics
Receptors, Transforming Growth Factor beta metabolism
Signal Transduction
Smad Proteins metabolism
Substrate Specificity
Interleukin-17 metabolism
Protein Kinase C-alpha metabolism
Th17 Cells immunology
Th17 Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4180
- Volume :
- 38
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 23290522
- Full Text :
- https://doi.org/10.1016/j.immuni.2012.09.021