TY - JOUR
T1 - IL-23 receptor regulation by Let-7f in human CD4+ memory T cells
AU - Li, Zhaoxia
AU - Wu, Feng
AU - Brant, Steven R.
AU - Kwon, John H.
PY - 2011/6/1
Y1 - 2011/6/1
N2 - CD4+ memory T cells include the Th17 cell population, which has been shown to be implicated in autoimmune and inflammatory diseases. These memory T cells express higher IL-23R and produce more IL-17 compared with their naive counterparts. However, the molecular mechanisms that regulate IL-23R expression in human T cells are not completely understood. MicroRNAs play important roles in a wide range of biological events through posttranscriptional suppression of target mRNAs. In this article, we provide evidence that a specific microRNA, Let-7f, inhibits IL-23R expression in human CD4+ memory T cells. Endogenous expression of Let-7f in memory T cells is significantly lower when compared with naive T cells, and Let-7f blocks IL-23R expression through its complementary target sequence within 3′ untranslated region of target gene. Furthermore, exogenous transfection of a Let-7f mimic into memory T cells results in downregulation of IL-23R and its downstream cytokine, IL-17. Our findings reveal a novel mechanism in regulating the IL-23/IL-23R pathway and subsequent downstream IL-17 production, which may provide novel therapeutics for human inflammatory and autoimmune diseases.
AB - CD4+ memory T cells include the Th17 cell population, which has been shown to be implicated in autoimmune and inflammatory diseases. These memory T cells express higher IL-23R and produce more IL-17 compared with their naive counterparts. However, the molecular mechanisms that regulate IL-23R expression in human T cells are not completely understood. MicroRNAs play important roles in a wide range of biological events through posttranscriptional suppression of target mRNAs. In this article, we provide evidence that a specific microRNA, Let-7f, inhibits IL-23R expression in human CD4+ memory T cells. Endogenous expression of Let-7f in memory T cells is significantly lower when compared with naive T cells, and Let-7f blocks IL-23R expression through its complementary target sequence within 3′ untranslated region of target gene. Furthermore, exogenous transfection of a Let-7f mimic into memory T cells results in downregulation of IL-23R and its downstream cytokine, IL-17. Our findings reveal a novel mechanism in regulating the IL-23/IL-23R pathway and subsequent downstream IL-17 production, which may provide novel therapeutics for human inflammatory and autoimmune diseases.
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U2 - 10.4049/jimmunol.1000917
DO - 10.4049/jimmunol.1000917
M3 - Article
C2 - 21508257
AN - SCOPUS:79958054292
SN - 0022-1767
VL - 186
SP - 6182
EP - 6190
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -