| First Author | Touma M | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 3 | Pages | 1681-92 |
| PubMed ID | 17641034 | Mgi Jnum | J:132071 |
| Mgi Id | MGI:3775053 | Doi | 10.4049/jimmunol.179.3.1681 |
| Citation | Touma M, et al. (2007) Functional role for I kappa BNS in T cell cytokine regulation as revealed by targeted gene disruption. J Immunol 179(3):1681-92 |
| abstractText | Triggering of the TCR by cognate peptide/MHC ligands induces expression of I kappa BNS, a member of the I kappa B family of NF-kappaB inhibitors whose expression is associated with apoptosis of immature thymocytes. To understand the role of I kappa BNS in TCR triggering, we created a targeted disruption of the I kappa BNS gene. Surprisingly, mice lacking I kappa BNS show normal thymic progression but both thymocytes and T cells manifest reduced TCR-stimulated proliferation. Moreover, I kappa BNS knockout thymocytes and T cells produce significantly less IL-2 and IFN-gamma than wild-type cells. Transfection analysis demonstrates that I kappa BNS and c-Rel individually increase IL-2 promoter activity. The effect of I kappa BNS on the IL-2 promoter, unlike c-Rel, is dependent on the NF-kappaB rather than the CD28RE site; mutation of the NF-kappaB site extinguishes the induction of transcription by I kappa BNS in transfectants and prevents association of I kappa BNS with IL-2 promoter DNA. Microarray analyses confirm the reduction in IL-2 production and some IFN-gamma-linked transcripts in I kappa BNS knockout T cells. Collectively, our findings demonstrate that I kappa BNS regulates production of IL-2 and other cytokines induced via 'strong' TCR ligation. |
