title: Upregulation of Tim-3 on CD4(+) T cells is associated with Th1/Th2 imbalance in patients with allergic asthma.
abstract: T cell Ig and mucin domain-containing molecule-3 (Tim-3) is a negative regulator preferentially expressed on Th1 cells. Allergic asthma is a clinical syndrome well characterized by Th1/Th2 imbalance. To investigate the role of Tim-3 in the pathogenesis of asthma and its relationship with Th1/Th2 imbalance, a total of 40 patients with allergic asthma and 40 healthy controls were enrolled. Expression of Tim-3 and Th1/Th2 imbalance as well as the relationship between them was analyzed by flow cytometry and real-time PCR. Peripheral blood mononuclear cells (PBMCs) were cultured in vitro and anti-Tim-3 was used to block Tim-3 signaling; Th1/Th2 cytokines in the culture supernatant were detected by enzyme linked immunosorbent assay (ELISA). CD4(+) T cells and B cells were sorted and co-cultured in vitro, and anti-Tim-3 was used to block Tim-3 signaling; Total IgG/IgE in the culture supernatant was detected by ELISA. The mRNA level of T-bet and IFN-γ were significantly decreased in allergic asthma patients, while GATA-3 and IL-4 were significantly increased. Expression of Tim-3 on CD4(+) T cells was much higher in allergic asthma patients and it was negatively correlated with T-bet/GATA-3 ratio or IFN-γ/IL-4 ratio. Blocking of Tim-3 significantly increased Th1 cytokines (TNF-α and IFN-γ) and decreased Th2 cytokines (IL-4, IL-5, IL-13) in the culture supernatant of PBMCs. Blocking of Tim-3 dramatically reduced the production of IgG and IgE in the co-culture supernatant of CD4(+) T cells and B cells. In conclusion, Tim-3 was up-regulated in allergic asthma patients and related with the Th1/Th2 imbalance. Blocking of Tim-3 may be of therapeutic benefit by enhancing the Th1 cytokines response, down-regulating the Th2 cytokines response, and reducing IgG/IgE production.
authors.affiliation: Department of Clinical Laboratory, Bethune International Peace Hospital of PLA 050082, Hebei Province, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Tang
authors.affiliation: Department of Clinical Laboratory, Bethune International Peace Hospital of PLA 050082, Hebei Province, China.
authors.forename: Fukun
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Bethune International Peace Hospital of PLA 050082, Hebei Province, China.
authors.forename: Liyun
authors.initials: L
authors.lastname: An
authors.affiliation: Department of Clinical Laboratory, Bethune International Peace Hospital of PLA 050082, Hebei Province, China.
authors.forename: Xianling
authors.initials: X
authors.lastname: Wang
keywords: Th1 cell; Th2 cell; Tim-3; asthma