The RING E3 ubiquitin ligase Trim13 (Rfp2) influences αβ and γδ T cell development (B5)

Abstract

Abstract αβ and γδ T cells arise from a common precursor in the thymus, but the mechanisms involved in this lineage specification remain poorly defined. We identified Tripartite Motif 13 (Trim13) as a γδ lineage biased gene. TRIM13, an RBCC protein, is an ER/nuclear membrane localized RING E3 ubiquitin ligase involved the ER-associated degradation pathway. Similar to other γδ lineage biased genes, the expression of Trim13 in γδ T cells is regulated in part by trans priming signals from αβ lineage DP thymocytes, and Trim13 is also expressed in some unconventional αβ lineage subsets. Interestingly, Trim13 is only expressed in about half of γδ thymocytes, suggesting that Trim13 may mark a subset of γδ T cells distinguishable by different thymic selection requirements, different stages of maturity, and/or functional competence. Preliminary results indicate that ectopic Trim13 expression is detrimental to αβ T cell development, but is conducive for enhanced γδ T cell generation and B cell development and/or expansion. These results suggest that Trim13 may play a role in T and B cell development, and that its expression may segregate specific subsets of T cells. Given its role as a nuclear membrane E3 ubiquitin ligase, it is possible that TRIM13 functions, in part, by controlling the relative abundance of transcription factors involved in lineage differentiation or maturation, resulting in different developmental outcomes.