TY - JOUR
T1 - CD4 + T cell-derived novel peptide Thp5 induces interleukin-4 production in CD4 + T cells to direct T helper 2 cell differentiation
AU - Khan, Mohd Moin
AU - Chatterjee, Samit
AU - Dwivedi, Ved Prakash
AU - Pandey, Nishant Kumar
AU - Singh, Yogesh
AU - Tousif, Sultan
AU - Bhavesh, Neel Sarovar
AU - Van Kaer, Luc
AU - Das, Jyoti
AU - Das, Gobardhan
PY - 2012/1/20
Y1 - 2012/1/20
N2 - The differentiation of naïve CD4 + T cells into T helper 2 (Th2) cells requires production of the cytokine IL-4 in the local microenvironment. It is evident that naïve/quiescently activated CD4 + T cells produce the IL-4 that drives Th2 cell differentiation. Because early production of IL-4 in naïve T cells leads to preferential Th2 cell differentiation, this process needs to be tightly regulated so as to avoid catastrophic and misdirected Th2 cell differentiation. Here, we show that Thp5, a novel peptide with structural similarity to vasoactive intestinal peptide, regulates production of early IL-4 in newly activated CD4 + T cells. Induction of IL-4 in CD4 + T cells by Thp5 is independent of the transcription factor STAT6 but dependent on ERK1/2 signaling. Furthermore, cytokines (IL-12 and TGF-β) that promote the differentiation of Th1 or Th17 cells inhibit Thp5 induction, thus suppressing Th2 cell differentiation. We further showed that Thp5 enhances Th2 responses and exacerbates allergic airway inflammation in mice. Taken together, our findings reveal that early activated CD4 + T cells produce Thp5, which plays a critical role as a molecular switch in the differentiation of Th cells, biasing the response toward the Th2 cell phenotype.
AB - The differentiation of naïve CD4 + T cells into T helper 2 (Th2) cells requires production of the cytokine IL-4 in the local microenvironment. It is evident that naïve/quiescently activated CD4 + T cells produce the IL-4 that drives Th2 cell differentiation. Because early production of IL-4 in naïve T cells leads to preferential Th2 cell differentiation, this process needs to be tightly regulated so as to avoid catastrophic and misdirected Th2 cell differentiation. Here, we show that Thp5, a novel peptide with structural similarity to vasoactive intestinal peptide, regulates production of early IL-4 in newly activated CD4 + T cells. Induction of IL-4 in CD4 + T cells by Thp5 is independent of the transcription factor STAT6 but dependent on ERK1/2 signaling. Furthermore, cytokines (IL-12 and TGF-β) that promote the differentiation of Th1 or Th17 cells inhibit Thp5 induction, thus suppressing Th2 cell differentiation. We further showed that Thp5 enhances Th2 responses and exacerbates allergic airway inflammation in mice. Taken together, our findings reveal that early activated CD4 + T cells produce Thp5, which plays a critical role as a molecular switch in the differentiation of Th cells, biasing the response toward the Th2 cell phenotype.
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U2 - 10.1074/jbc.M111.319947
DO - 10.1074/jbc.M111.319947
M3 - Article
C2 - 22130674
AN - SCOPUS:84863418649
VL - 287
SP - 2830
EP - 2835
JO - The Journal of biological chemistry
JF - The Journal of biological chemistry
SN - 0021-9258
IS - 4
ER -