PRMT5 Is Required for T Cell Survival and Proliferation by Maintaining Cytokine Signaling
Arginine methylation is a post-translational modification that regulates many biological processes. However, the role of arginine methylation in immune cells is not well studied. Here we report an essential role of protein arginine methyltransferase 5 (PRMT5) in T cell homeostasis and activation-ind...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-04-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00621/full |
| _version_ | 1819230113928052736 |
|---|---|
| author | Yukinori Tanaka Yasuhiro Nagai Mariko Okumura Mark I. Greene Taku Kambayashi |
| author_facet | Yukinori Tanaka Yasuhiro Nagai Mariko Okumura Mark I. Greene Taku Kambayashi |
| author_sort | Yukinori Tanaka |
| collection | DOAJ |
| description | Arginine methylation is a post-translational modification that regulates many biological processes. However, the role of arginine methylation in immune cells is not well studied. Here we report an essential role of protein arginine methyltransferase 5 (PRMT5) in T cell homeostasis and activation-induced expansion. Using T cell-specific PRMT5 conditional knockout mice, we found that PRMT5 is required for natural killer T (NKT) cell but not for conventional or regulatory T (Treg) cell development after the double positive (DP) stage in the thymus. In contrast, PRMT5 was required for optimal peripheral T cell maintenance, for the transition of naïve T cells to effector/memory phenotype, and for early T cell development before the DP stage in a cell-intrinsic manner. Accordingly, PRMT5-deleted T cells showed impaired IL-7-mediated survival and TCR-induced proliferation in vitro. The latter was more pronounced and attributed to reduced responsiveness to IL-2. Acute deletion of PRMT5 revealed that not only naïve but also effector/memory T cells were impaired in TCR-induced proliferation in a development-independent manner. Reduced expression of common γ chain (γc), a shared receptor component for several cytokines including IL-7 and IL-2, on PRMT5-deleted T cells may be in part responsible for the defect. We further showed that PRMT5 was partially required for homeostatic T cell survival but absolutely required for lymphopenic T cell expansion in vivo. Thus, we propose that PRMT5 is required for T cell survival and proliferation by maintaining cytokine signaling, especially during proliferation. The inhibition of PRMT5 may provide a novel strategy for the treatment of diseases where uncontrolled T cell activation has a role, such as autoimmunity. |
| first_indexed | 2024-12-23T11:23:55Z |
| format | Article |
| id | doaj.art-9cc1475e701646cb9ad27cae33076719 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T11:23:55Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9cc1475e701646cb9ad27cae330767192022-12-21T17:49:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-04-011110.3389/fimmu.2020.00621508645PRMT5 Is Required for T Cell Survival and Proliferation by Maintaining Cytokine SignalingYukinori TanakaYasuhiro NagaiMariko OkumuraMark I. GreeneTaku KambayashiArginine methylation is a post-translational modification that regulates many biological processes. However, the role of arginine methylation in immune cells is not well studied. Here we report an essential role of protein arginine methyltransferase 5 (PRMT5) in T cell homeostasis and activation-induced expansion. Using T cell-specific PRMT5 conditional knockout mice, we found that PRMT5 is required for natural killer T (NKT) cell but not for conventional or regulatory T (Treg) cell development after the double positive (DP) stage in the thymus. In contrast, PRMT5 was required for optimal peripheral T cell maintenance, for the transition of naïve T cells to effector/memory phenotype, and for early T cell development before the DP stage in a cell-intrinsic manner. Accordingly, PRMT5-deleted T cells showed impaired IL-7-mediated survival and TCR-induced proliferation in vitro. The latter was more pronounced and attributed to reduced responsiveness to IL-2. Acute deletion of PRMT5 revealed that not only naïve but also effector/memory T cells were impaired in TCR-induced proliferation in a development-independent manner. Reduced expression of common γ chain (γc), a shared receptor component for several cytokines including IL-7 and IL-2, on PRMT5-deleted T cells may be in part responsible for the defect. We further showed that PRMT5 was partially required for homeostatic T cell survival but absolutely required for lymphopenic T cell expansion in vivo. Thus, we propose that PRMT5 is required for T cell survival and proliferation by maintaining cytokine signaling, especially during proliferation. The inhibition of PRMT5 may provide a novel strategy for the treatment of diseases where uncontrolled T cell activation has a role, such as autoimmunity.https://www.frontiersin.org/article/10.3389/fimmu.2020.00621/fullarginine methylationPRMT5T cell survivalT cell proliferationT cell developmentcytokine signaling |
| spellingShingle | Yukinori Tanaka Yasuhiro Nagai Mariko Okumura Mark I. Greene Taku Kambayashi PRMT5 Is Required for T Cell Survival and Proliferation by Maintaining Cytokine Signaling Frontiers in Immunology arginine methylation PRMT5 T cell survival T cell proliferation T cell development cytokine signaling |
| title | PRMT5 Is Required for T Cell Survival and Proliferation by Maintaining Cytokine Signaling |
| title_full | PRMT5 Is Required for T Cell Survival and Proliferation by Maintaining Cytokine Signaling |
| title_fullStr | PRMT5 Is Required for T Cell Survival and Proliferation by Maintaining Cytokine Signaling |
| title_full_unstemmed | PRMT5 Is Required for T Cell Survival and Proliferation by Maintaining Cytokine Signaling |
| title_short | PRMT5 Is Required for T Cell Survival and Proliferation by Maintaining Cytokine Signaling |
| title_sort | prmt5 is required for t cell survival and proliferation by maintaining cytokine signaling |
| topic | arginine methylation PRMT5 T cell survival T cell proliferation T cell development cytokine signaling |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00621/full |
| work_keys_str_mv | AT yukinoritanaka prmt5isrequiredfortcellsurvivalandproliferationbymaintainingcytokinesignaling AT yasuhironagai prmt5isrequiredfortcellsurvivalandproliferationbymaintainingcytokinesignaling AT marikookumura prmt5isrequiredfortcellsurvivalandproliferationbymaintainingcytokinesignaling AT markigreene prmt5isrequiredfortcellsurvivalandproliferationbymaintainingcytokinesignaling AT takukambayashi prmt5isrequiredfortcellsurvivalandproliferationbymaintainingcytokinesignaling |