Impact Of PI3K And STAT6 On T Lymphocytes' Proliferation In Bronchial Asthma

Objective: To explore the impact of PI3K and STAT6 on T lymphocyte subsets' proliferation in bronchial asthma and find out a new way in target therapy of asthma by intervening CD4~+T and CD8~+T lymphocytes' proliferation with the inhibitors of PI3K orJAK1-STAT6 signal pathway. Methods: (l)The changes of cell cycle distribution inCD4~+T and CD8~+T lymphocytes of asthmatic subjects, subjects in clinical remission and healthy control subjects were investigated, together with the expression levels of cell cycle regulatory proteins(CCRP) , phosphoinositide 3-kinase (PI3K) and signal transducer and activator of transcription 6(STAT6); The differences between the CD4~+T and CD8~+T lymphocytes were compared, too.(2) It was measured the changes of cell cycle distribution in CD4~+T and CD8~+T lymphocytes of asthmatic subjects under the intervening of the inhibitor of PI3K or STAT6, ie LY294002 or IFN-γ , the expression levels of CCRP, PI3K and STAT6were studied at the same time. Results:(1) The CD4~+T or CD8~+T lymphocytes'proliferation differed significantly among asthmatic subjects, subjects in clinical remission and healthy control subjects. The percentages of CD4~+T or CD8~+T lymphocytes during the proliferative stage from asthmatic subjects were higher than those from healthy control subjects or subjects in clinical remission. The percentages of proliferative stage in CD4~+T lymphocytes from subjects in clinical remission were higher than those from healthy control subjects. Most of the CD4~+T or CD8~+T lymphocytes from healthy control subjects were in the stable stage. (2) The PI3K signal pathway can promote the activation and proliferation of the CD4~+T or CD8~+T lymphocytes by upregulating CyclinD and/or CyclinE , while the JAK1-STAT6 signal pathway can do it by downregulating P27~kip1. The excess proliferation of CD4~+T lymphocytes from subjects in clinical remission was due to the upregulation of PI3K which lead to the increase of CyclinD and CyclinE. (3) LY294002 and IFN- y can inhibite the PI3K and STAT6 signal pathway respectively, and the expression levels of CCRP wereaffected as a result, which influenced the cell cycle distribution at last. Concllltion:Theintervention to the PI3K and STAT6 can be a new and promise therapy target in the treatment of asthma., Further studies are necessary to explore what is the exact relationship between the PI3K and the JAK1-STAT6 signal pathway during the enhancement of CD4+T or CD8+T lymphocytes' proliferation in bronchial asthma.