Journal
IMMUNOLOGY
Volume 129, Issue 4, Pages 589-599Publisher
WILEY
DOI: 10.1111/j.1365-2567.2009.03161.x
Keywords
anergy; signalling; signal transduction; T cells; tolerance
Categories
Funding
- National Science Foundation
- Arkansas Biosciences Institute
- UAMS Graduate Student Research Funds
Ask authors/readers for more resources
P>Histone deacetylase inhibitor n-butyrate induced proliferative unresponsiveness in antigen-stimulated murine CD4+ T cells. T cells anergized by n-butyrate demonstrated reduced interleukin-2 (IL-2) secretion and decreased activating protein 1 (AP-1) activity upon restimulation. Mechanistic studies determined that the cyclin-dependent kinase (cdk) inhibitor p21Cip1 was up-regulated in the anergic CD4+ T cells. p21Cip1 is known to inhibit the cell cycle through its interaction with cdk, proliferating cell nuclear antigen (PCNA) or c-Jun N-terminal kinase (JNK). p21Cip1 did not preferentially associate with PCNA or cdk in anergic T helper type 1 (Th1) cells. Instead, among the three interaction partners, p21Cip1 was found to interact with phospho-JNK and phospho-c-jun selectively in the anergic CD4+ T cells. The activity of c-jun and downstream transcription factor AP-1 were suppressed in the anergic Th1 cells. In contrast, p21Cip1 and the two phospho-proteins were never detected concurrently in the control CD4+ T cells. The n-butyrate-induced p21Cip1-mediated inhibition of JNK and c-jun represents a novel potential mechanism by which proliferative unresponsiveness was maintained in CD4+ T cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available