Journal
JOURNAL OF IMMUNOLOGY
Volume 202, Issue 10, Pages 3008-3019Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1801614
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Funding
- National Nature Science Foundation of China [81630058, 81570211, 91542107, 31670904]
- Tsinghua University-Peking University Center for Life Sciences
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The paracaspase Malt1 is a key molecule in mediating Ag receptor-induced NF-kappa B 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 Maltl 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 inflam-matory 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 Maltl 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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