| First Author | Cheng L | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 10 | Pages | 3008-3019 |
| PubMed ID | 30979818 | Mgi Jnum | J:274896 |
| Mgi Id | MGI:6296854 | Doi | 10.4049/jimmunol.1801614 |
| Citation | Cheng L, et al. (2019) Malt1 Protease Is Critical in Maintaining Function of Regulatory T Cells and May Be a Therapeutic Target for Antitumor Immunity. J Immunol 202(10):3008-3019 |
| abstractText | The paracaspase Malt1 is a key molecule in mediating Ag receptor-induced NF-kappaB 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, Foxp3(Cre)Malt1(fl/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, Foxp3(Cre)Malt1(fl/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. |
