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Publication Abstract from PubMed

The differentiation of naive CD4+ T cells into T helper 2 (Th2) cells requires production of the cytokine IL-4 in the local microenvironment. It is evident that naive/quiescently activated CD4+ T cells produce the IL-4 that drives Th2 cell differentiation. Because early production of IL-4 in naive 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 (VIP), 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 Erk-1/2 signaling. Furthermore, cytokines (IL-12 and TGF-beta) 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 (AAI) 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 towards the Th2 cell phenotype.

CD4+ T cell derived novel peptide Thp5 induces IL-4 production in CD4+ T cells to direct T helper 2 cell differentiation.,Khan MM, Chatterjee S, Dwivedi VP, Pandey NK, Singh Y, Tousif S, Bhavesh NS, Kaer LV, Das J, Das G J Biol Chem. 2011 Nov 30. PMID:22130674^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.