| First Author | Tarasenko TN | Year | 2015 |
| Journal | J Leukoc Biol | Volume | 97 |
| Issue | 2 | Pages | 273-8 |
| PubMed ID | 25492936 | Mgi Jnum | J:220401 |
| Mgi Id | MGI:5634618 | Doi | 10.1189/jlb.1AB0714-365R |
| Citation | Tarasenko TN, et al. (2015) Impaired T cell function in argininosuccinate synthetase deficiency. J Leukoc Biol 97(2):273-8 |
| abstractText | ASS1 is a cytosolic enzyme that plays a role in the conversion of citrulline to arginine. In human and mouse tissues, ASS1 protein is found in several components of the immune system, including the thymus and T cells. However, the role of ASS1 in these tissues remains to be defined. Considerable attention has been focused recently on the role of metabolism in T cell differentiation and function. Based on the expression of ASS1 in the immune system, we hypothesized that ASS1 deficiency would result in T cell defects. To evaluate this question, we characterized immune function in hypomorphic fold/fold mice. Analysis of splenic T cells by flow cytometry showed a marked reduction in T cell numbers with normal expression of activation surface markers. Gene therapy correction of liver ASS1 to enhance survival resulted in a partial recovery of splenic T cells for characterization. In vitro and in vivo studies demonstrated the persistence of the ASS1 enzyme defect in T cells and abnormal T cell differentiation and function. Overall, our work suggests that ASS1 plays a role in T cell function, and deficiency produces primary immune dysfunction. In addition, these data suggest that patients with ASS1 deficiency (citrullinemia type I) may have T cell dysfunction. |
