Malt1 Protease Is Critical in Maintaining Function of Regulatory T Cells and May Be a Therapeutic Target for Antitumor Immunity.
Liqing ChengNan DengNaixue YangXueqiang ZhaoXin LinPublished in: Journal of immunology (Baltimore, Md. : 1950) (2019)
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.
Keyphrases
- regulatory t cells
- induced apoptosis
- cell cycle arrest
- oxidative stress
- endoplasmic reticulum stress
- multiple sclerosis
- poor prognosis
- dendritic cells
- genome wide
- cell proliferation
- machine learning
- pi k akt
- transcription factor
- adipose tissue
- high fat diet induced
- peripheral blood
- endothelial cells
- quantum dots
- cell therapy
- big data
- high glucose
- highly efficient
- bioinformatics analysis