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GIT2 deficiency attenuates concanavalin A-induced hepatitis in mice.

Hao YE, He DF, Yin RH, Chen H, Wang J, Wang SX, Zhan YQ, Ge CH, Li CY, Yu M, Yang XM - FEBS Open Bio (2015)

Bottom Line: G protein-coupled receptor kinase interactor 2 (GIT2) is a signaling scaffold protein involved in regulation of cytoskeletal dynamics and the internalization of G protein-coupled receptors (GPCRs).However, the functions of GIT2 in T cells have not yet been determined.Our results suggested that GIT2 plays an important role in T-cell function in vivo and in vitro.

View Article: PubMed Central - PubMed

Affiliation: Southern Medical University, Guangzhou, Guangdong Province, China ; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.

ABSTRACT
G protein-coupled receptor kinase interactor 2 (GIT2) is a signaling scaffold protein involved in regulation of cytoskeletal dynamics and the internalization of G protein-coupled receptors (GPCRs). The short-splice form of GIT2 is expressed in peripheral T cells and thymocytes. However, the functions of GIT2 in T cells have not yet been determined. We show that treatment with Con A in a model of polyclonal T-lymphocyte activation resulted in marked inhibitions in the intrahepatic infiltration of inflammatory cells, cytokine response and acute liver failure in Git2 (-/-) mice. CD4(+) T cells from Git2 (-/-) mice showed significant impairment in proliferation, cytokine production and signal transduction upon TCR-stimulated activation. Our results suggested that GIT2 plays an important role in T-cell function in vivo and in vitro.

No MeSH data available.


Related in: MedlinePlus

GIT2 depletion suppressed lymphoid cells infiltration to liver after Con A treatment. Liver MNC and splenocyte from Git2+/+ and Git2−/− mice (n = 6) were isolated at 6 h after 15 mg/kg Con A injection. (A) Cell numbers of total liver MNC, CD4+, CD8+, CD19+, NK, and NKT were quantified. (B) Cell numbers and percentage of Tregs were quantified. (C) Cell numbers of total splenocyte, splenic CD4+, splenic Tregs and Tregs percentage were quantified. (D) Cells were labeled with PI and annexin V–FITC and then analyzed by FACS. The results were representative of three independent experiments and error bars represent standard deviations (*P < 0.05, **P < 0.01).
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f0015: GIT2 depletion suppressed lymphoid cells infiltration to liver after Con A treatment. Liver MNC and splenocyte from Git2+/+ and Git2−/− mice (n = 6) were isolated at 6 h after 15 mg/kg Con A injection. (A) Cell numbers of total liver MNC, CD4+, CD8+, CD19+, NK, and NKT were quantified. (B) Cell numbers and percentage of Tregs were quantified. (C) Cell numbers of total splenocyte, splenic CD4+, splenic Tregs and Tregs percentage were quantified. (D) Cells were labeled with PI and annexin V–FITC and then analyzed by FACS. The results were representative of three independent experiments and error bars represent standard deviations (*P < 0.05, **P < 0.01).

Mentions: To examine whether GIT2 depletion affects the influx of MNCs in the liver after Con A injection, we first analyzed the steady-state composition of immune cells in the liver of Git2−/− mice. The liver MNCs were isolated and subjected to flow cytometry analysis. As shown in Fig. 3A, the total number of mononuclear cells in the liver of Git2−/− mice was equal to that in Git2+/+ mice. However, the numbers of basal CD4+ T cells and NKT cells were significantly reduced in the liver of Git2−/− mice, whereas the CD8+ cells were increased compared with the Git2+/+ controls. Other liver MNC subsets, such as NK cells and B cells, were not influenced (Fig. 3A).


GIT2 deficiency attenuates concanavalin A-induced hepatitis in mice.

Hao YE, He DF, Yin RH, Chen H, Wang J, Wang SX, Zhan YQ, Ge CH, Li CY, Yu M, Yang XM - FEBS Open Bio (2015)

GIT2 depletion suppressed lymphoid cells infiltration to liver after Con A treatment. Liver MNC and splenocyte from Git2+/+ and Git2−/− mice (n = 6) were isolated at 6 h after 15 mg/kg Con A injection. (A) Cell numbers of total liver MNC, CD4+, CD8+, CD19+, NK, and NKT were quantified. (B) Cell numbers and percentage of Tregs were quantified. (C) Cell numbers of total splenocyte, splenic CD4+, splenic Tregs and Tregs percentage were quantified. (D) Cells were labeled with PI and annexin V–FITC and then analyzed by FACS. The results were representative of three independent experiments and error bars represent standard deviations (*P < 0.05, **P < 0.01).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556731&req=5

f0015: GIT2 depletion suppressed lymphoid cells infiltration to liver after Con A treatment. Liver MNC and splenocyte from Git2+/+ and Git2−/− mice (n = 6) were isolated at 6 h after 15 mg/kg Con A injection. (A) Cell numbers of total liver MNC, CD4+, CD8+, CD19+, NK, and NKT were quantified. (B) Cell numbers and percentage of Tregs were quantified. (C) Cell numbers of total splenocyte, splenic CD4+, splenic Tregs and Tregs percentage were quantified. (D) Cells were labeled with PI and annexin V–FITC and then analyzed by FACS. The results were representative of three independent experiments and error bars represent standard deviations (*P < 0.05, **P < 0.01).
Mentions: To examine whether GIT2 depletion affects the influx of MNCs in the liver after Con A injection, we first analyzed the steady-state composition of immune cells in the liver of Git2−/− mice. The liver MNCs were isolated and subjected to flow cytometry analysis. As shown in Fig. 3A, the total number of mononuclear cells in the liver of Git2−/− mice was equal to that in Git2+/+ mice. However, the numbers of basal CD4+ T cells and NKT cells were significantly reduced in the liver of Git2−/− mice, whereas the CD8+ cells were increased compared with the Git2+/+ controls. Other liver MNC subsets, such as NK cells and B cells, were not influenced (Fig. 3A).

Bottom Line: G protein-coupled receptor kinase interactor 2 (GIT2) is a signaling scaffold protein involved in regulation of cytoskeletal dynamics and the internalization of G protein-coupled receptors (GPCRs).However, the functions of GIT2 in T cells have not yet been determined.Our results suggested that GIT2 plays an important role in T-cell function in vivo and in vitro.

View Article: PubMed Central - PubMed

Affiliation: Southern Medical University, Guangzhou, Guangdong Province, China ; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.

ABSTRACT
G protein-coupled receptor kinase interactor 2 (GIT2) is a signaling scaffold protein involved in regulation of cytoskeletal dynamics and the internalization of G protein-coupled receptors (GPCRs). The short-splice form of GIT2 is expressed in peripheral T cells and thymocytes. However, the functions of GIT2 in T cells have not yet been determined. We show that treatment with Con A in a model of polyclonal T-lymphocyte activation resulted in marked inhibitions in the intrahepatic infiltration of inflammatory cells, cytokine response and acute liver failure in Git2 (-/-) mice. CD4(+) T cells from Git2 (-/-) mice showed significant impairment in proliferation, cytokine production and signal transduction upon TCR-stimulated activation. Our results suggested that GIT2 plays an important role in T-cell function in vivo and in vitro.

No MeSH data available.


Related in: MedlinePlus