| First Author | Muthusamy N | Year | 2011 |
| Journal | Int Immunol | Volume | 23 |
| Issue | 6 | Pages | 385-90 |
| PubMed ID | 21602176 | Mgi Jnum | J:172747 |
| Mgi Id | MGI:5008693 | Doi | 10.1093/intimm/dxr025 |
| Citation | Muthusamy N, et al. (2011) Recombination activation gene-2-deficient blastocyst complementation analysis reveals an essential role for nuclear factor I-A transcription factor in T-cell activation. Int Immunol 23(6):385-90 |
| abstractText | Nuclear factor I (NFI)-A is a member of the NFI family of transcription factors implicated in regulation of granulocyte differentiation. However, its role in the lymphoid lineage is not known. NFI-A deficiency results in perinatal lethality, thus precluding analysis of the role of NFI-A in lymphocyte development and function. Using recombination activation gene-2-deficient (RAG-2(-/-)) blastocysts and embryonic stem cells with homozygous NFI-A gene deletion, we show an essential role for NFI-A in T-cell activation. NFI-A(-/-)-->RAG-2(-/-) chimeric mice had normal distributions of CD4(-)CD8(-) double negative, CD4(+)CD8(+) double positive, CD4(+)CD8(-) and CD4(-)CD8(+)-single positive cells in the thymus and CD4(+)CD8(-) and CD4(-)CD8(+) cells in spleen and lymph nodes. However, NFI-A(-/-)-->RAG-2(-)(/)(-) mice had severely reduced thymus size and hypocellularity. The decrease in thymocytes and peripheral T cells in NFI-A(-/-)-->RAG-2(-/-) chimeric mice is attributed to proliferative defects associated with decreased blast transformation, CD69 expression and DNA synthesis in response to T antigen receptor stimulation. Interestingly, NFI-A-null T cells showed increased levels of c-myc transcription that is inhibited in response to antigen receptor-mediated activation. These studies demonstrate for the first time a requirement for the NFI-A transcription factor in antigen receptor-induced T-cell activation events. |
