Article ; Online: Phosphorylation of hnRNP A1-Serine 199 Is Not Required for T Cell Differentiation and Function.
ImmunoHorizons
2024 Volume 8, Issue 2, Page(s) 136–146
Abstract: hnRNP A1 is an important RNA-binding protein that influences many stages of RNA processing, including transcription, alternative splicing, mRNA nuclear export, and RNA stability. However, the role of hnRNP A1 in immune cells, specifically CD4+ T cells, ... ...
| Abstract | hnRNP A1 is an important RNA-binding protein that influences many stages of RNA processing, including transcription, alternative splicing, mRNA nuclear export, and RNA stability. However, the role of hnRNP A1 in immune cells, specifically CD4+ T cells, remains unclear. We previously showed that Akt phosphorylation of hnRNP A1 was dependent on TCR signal strength and was associated with Treg differentiation. To explore the impact of hnRNP A1 phosphorylation by Akt on CD4+ T cell differentiation, our laboratory generated a mutant mouse model, hnRNP A1-S199A (A1-MUT) in which the major Akt phosphorylation site on hnRNP A1 was mutated to alanine using CRISPR Cas9 technology. Immune profiling of A1-MUT mice revealed changes in the numbers of Tregs in the mesenteric lymph node. We found no significant differences in naive CD4+ T cell differentiation into Th1, Th2, Th17, or T regulatory cells (Tregs) in vitro. In vivo, Treg differentiation assays using OTII-A1-Mut CD4+ T cells exposed to OVA food revealed migration and homing defects in the A1-MUT but no change in Treg induction. A1-MUT mice were immunized with NP- keyhole limpet hemocyanin, and normal germinal center development, normal numbers of NP-specific B cells, and no change in Tfh numbers were observed. In conclusion, Akt phosphorylation of hnRNP A1 S199 does not play a role in CD4+ T cell fate or function in the models tested. This hnRNP A1-S199A mouse model should be a valuable tool to study the role of Akt phosphorylation of hnRNP A1-S199 in different cell types or other mouse models of human disease. |
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| MeSH term(s) | Animals ; Mice ; Cell Differentiation ; Heterogeneous Nuclear Ribonucleoprotein A1/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Receptors, Antigen, T-Cell/metabolism ; Serine/metabolism ; Signal Transduction ; T-Lymphocytes/cytology |
| Chemical Substances | Heterogeneous Nuclear Ribonucleoprotein A1 ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Receptors, Antigen, T-Cell ; Serine (452VLY9402) |
| Language | English |
| Publishing date | 2024-02-09 |
| Publishing country | United States |
| Document type | Journal Article |
| ISSN | 2573-7732 |
| ISSN (online) | 2573-7732 |
| DOI | 10.4049/immunohorizons.2300074 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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