T cell-specific disruption of arylhydrocarbon receptor nuclear translocator (Arnt) gene causes resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced thymic involution
Tomita, S; Jiang, HB; Ueno, T; Takagi, S; Tohi, K; Maekawa, S; Miyatake, A; Furukawa, A; Gonzalez, FJ; Takeda, J; Ichikawa, Y; Takahama, Y
HERO ID
199194
Reference Type
Journal Article
Year
2003
Language
English
PMID
| HERO ID | 199194 |
|---|---|
| In Press | No |
| Year | 2003 |
| Title | T cell-specific disruption of arylhydrocarbon receptor nuclear translocator (Arnt) gene causes resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced thymic involution |
| Authors | Tomita, S; Jiang, HB; Ueno, T; Takagi, S; Tohi, K; Maekawa, S; Miyatake, A; Furukawa, A; Gonzalez, FJ; Takeda, J; Ichikawa, Y; Takahama, Y |
| Journal | Journal of Immunology |
| Volume | 171 |
| Issue | 8 |
| Page Numbers | 4113-4120 |
| Abstract | The arylhydrocarbon receptor nuclear translocator (ARNT) is a member of the basic helix-loop-helix, PER-ARNT-SIM family of heterodimeric transcription factors, and serves as a dimerization partner for arylhydrocarbon receptor (AHR) and hypoxia-inducible factor-1alpha. To assess the function of ARNT in T cells, we disrupted the Arnt gene specifically in T cells of mice by conditional gene targeting using T cell-specific p56(lck)-Cre (Lck-Cre) transgenic Arnt-floxed mice. Thus generated, T cell-specific Arnt-disrupted mice (Lck-Cre;Arnt(flox/Delta) transgenic mice) exhibited complete loss of the expression of ARNT protein only in T cells, and were viable and appeared normal. The Arnt-disrupted T cells in the thymus were phenotypically and histologically normal. The Arnt-deficient T cells in the spleen were capable of responding to TCR stimulation in vitro. However, unlike normal mice in which exposure to the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an AHR ligand, resulted in thymic involution, the thymus of Lck-Cre;Arnt(flox/Delta) mice were resistant to TCDD treatment in vivo. In contrast, benzo(a)pyrene, another AHR ligand, still caused thymic involution in Lck-Cre;Arnt(flox/Delta) mice. Finally, fetal thymus organ culture using Lck-Cre;Arnt(flox/Delta) and K5-Cre;Arnt(flox/Delta) (epithelial cell-specific Arnt-disrupted mice) showed that thymocytes rather than thymic epithelial cells are predominantly responsible for TCDD-induced thymic atrophy. Our results indicate that ARNT in T lineage cells is essential for TCDD-mediated thymic involution. |
| Doi | 10.4049/jimmunol.171.8.4113 |
| Pmid | 14530333 |
| Wosid | WOS:000185866100027 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-0141923738&doi=10.4049%2fjimmunol.171.8.4113&partnerID=40&md5=21215b754fcfedd3289d4741e69f38df |
| Is Public | Yes |
| Language Text | English |
| Is Qa | No |