The Journal of Immunology · 2019 · 51 citations · 52 references
Life SciencesImmunologyOncologyAutoimmunityImmunoregulationInflammationAntitumor T Cell ResponsesImmune Gene RegulationRegulatory T Cell DysfunctionRegulatory T CellsT Cell BiologyT Cell ExhaustionAntitumor Immune ActivationCd8 Positive T Cell ResponsesCd8 T Cell ActivationHair Loss PathogenesisNf-κb SignalingPeripheral Regulatory T CellsProtease InactivationTreg Cell Homeostasis
Abstract The paracaspase Malt1 is a key molecule in mediating Ag receptor–induced NF-κB activation in lymphocytes, but the role of Malt1 in the function of regulatory T (Treg) cells is still unclear. In this article, we reported that specific deletion of Malt1 in Treg cells would lead to Scurfy-like lethal autoimmune disease, which was caused by Treg cell dysfunction but not number loss. Interestingly, Foxp3CreMalt1fl/C472A mice, in which Malt1 protease was specifically inactivated in Treg cells, also displayed spontaneous inflammatory disorders, with severe hair loss and skin hyperplasia. Consistently, Foxp3CreMalt1fl/C472A mice showed enhanced antitumor response because of their decreased function and infiltration of Treg cells, as well as reduced CD8+ T cell exhaustion. Gene expression profiling analysis revealed dysregulated expression pattern of Treg effector genes upon Malt1 deletion or its protease inactivation. Together, our data unraveled a critical role of Malt1, especially its protease activity, in maintaining homeostasis and function of Treg cells.
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