IndraLab

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USP15 activates IFNG. 8 / 8
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"These findings suggest that T cell intrinsic USP15 deficiency causes excessive production of IFN-gamma, which promotes an immunosuppressive tumor microenvironment, during MCA induced primary tumorigenesis."
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"Our present study revealed that in the MCA induced fibrosarcoma model, USP15 deficiency caused hyper-activation of IFN-gamma + T cells, which was associated with formation of a more immunosuppressive tumor microenvironment characterized by upregulated expression of PD-L1 and CXCL12 and enhanced recruitment of Treg cells and MDSCs."
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"To determine the source of the aberrantly higher level of serum IFN-gamma in Usp15 -/- mice, we examined whether the USP15 deficiency promoted IFN-gamma production in T cells or innate immune cells at the tumor site."
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"found that USP15 was abundantly expressed in immune cells, and the USP15 deficiency promoted the TCR + CD28 - stimulated production of cytokines, such as interleukin 2 (IL-2) and interferon-gamma in naive CD4 + T cells."
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"However, since the development of primary tumors involves a long period of interplays between tumors and the immune system, it has remained unclear how the excessive and chronic production of IFN-gamma by USP15 deficient T cells impacts the development of primary tumors."
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"Moreover, excessive IFN-gamma production by USP15 deficient CD4 + T cells promoted the expression of CXCL12 leading to an accumulation of T-bet + Treg cells and CD11b + Gr-1 + MDSC, therefore promoting MCA induced tumorigenesis [XREF_BIBR]."
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"However, the USP15 deficiency promoted the TCR+CD 28 stimulated production of cytokines, such as interleukin 2 (IL-2) and interferon-gamma (IFN-gamma), in naive CD4 + T cells, as assessed by quantitative real-time RT-PCR (qRT-PCR) (XREF_FIG), intracellular cytokine staining (XREF_FIG) and ELISA (XREF_FIG)."
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"T cell intrinsic USP15 deficiency promotes excessive IFN-gamma production and an immunosuppressive tumor microenvironment in MCA induced fibrosarcoma."
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