PRMT5: splicing up tolerance
Rathan Kumar, Parvathi Ranganathan
Rathan Kumar, Parvathi Ranganathan
Published October 15, 2024
Citation Information: J Clin Invest. 2024;134(20):e185701. https://doi.org/10.1172/JCI185701.
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Commentary

PRMT5: splicing up tolerance

Abstract

Expression of tissue-restricted antigens (TRAs) within the thymus is critical for the establishment of self-tolerance; however, exact mechanisms regulating the expression of TRAs has proven more complex than previously appreciated. In this issue of the JCI, Muro et al. identify a central role for protein arginine methyltransferase 5 (PRMT5) in posttranscriptional regulation of TRAs and thereby central tolerance. Using conditional KO mice, the authors showed that thymic deficiency of Prmt5 predisposed mice to developing autoimmune diseases while enhancing antitumor efficacy. These studies provide insight into the role of PRMT5 in shaping the T cell repertoire with implications for the development of therapies.

Authors

Rathan Kumar, Parvathi Ranganathan

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Figure 1

Muro et al. present a role of mTEC-expressed PRMT5 in shaping immune tolerance.

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Muro et al. present a role of mTEC-expressed PRMT5 in shaping immune tol...
(A) In mTECs expressing WT PRMT5, intact splicing generates a diverse range of TRA expression and presentation, resulting in clonal deletion of self-reactive T cells and the generation of a self-tolerant T cell repertoire. (B) Conditional deletion of Prmt5 in mTECs results in reduced spliceosome efficiency and increased intron retention, leading to decreased TRA expression. The resulting T cell repertoire included self-reactive T cells and thus a predisposition toward autoimmunity as well as enhanced antitumor function.