title: CD4+ T cell-derived novel peptide Thp5 induces interleukin-4 production in CD4+ T cells to direct T helper 2 cell differentiation.
abstract: 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.
authors: Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors: Mohd Moin
authors: MM
authors: Khan
authors: Samit
authors: S
authors: Chatterjee
authors: Ved Prakash
authors: VP
authors: Dwivedi
authors: Nishant Kumar
authors: NK
authors: Pandey
authors: Yogesh
authors: Y
authors: Singh
authors: Sultan
authors: S
authors: Tousif
authors: Neel Sarovar
authors: NS
authors: Bhavesh
authors: Luc
authors: L
authors: Van Kaer
authors: Jyoti
authors: J
authors: Das
authors: Gobardhan
authors: G
authors: Das
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000276:immunology / Q000378:metabolism
chemical_list: D010455:Peptides; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C570673:Thp5 peptide; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D015847:Interleukin-4; D014660:Vasoactive Intestinal Peptide