Suppression of IL7Rα transcription by IL-7 and other prosurvival cytokines:: A novel mechanism for maximizing IL-7-dependent T cell survival

Park J., Yu Q., ERMAN M. B., Appelbaum J., Montoya-Durango D., Grimes J., ...Daha Fazla

IMMUNITY, cilt.21, sa.2, ss.289-302, 2004 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 21 Sayı: 2
  • Basım Tarihi: 2004
  • Doi Numarası: 10.1016/j.immuni.2004.07.016
  • Dergi Adı: IMMUNITY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.289-302
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Hayır

Özet

Survival of naive T cells is dependent upon IL-7, which is present in vivo in limiting amounts with the result that naive T cells must compete for IL-7-mediated survival signals. It would seem imperative during T cell homeostasis that limiting IL-7 be shared by the greatest possible number of T cells. We now describe a novel regulatory mechanism that specifically suppresses IL7Ralpha transcription in response to IL-7 and other prosurvival cytokines (IL-2, IL-4, IL-6, and IL-15). Consequently, IL7R expression is reduced on T cells that have received cytokine-mediated survival signals so they do not compete with unsignaled T cells for remaining IL-7. Interestingly, cytokine-mediated suppression of IL7Ralpha transcription involves different molecular mechanisms in CD4(+) and CD8(+) T cells, as CD8(+) T cells utilize the transcriptional repressor GFI1 while CD4(+) T cells do not. We suggest that this homeostatic regulatory mechanism promotes survival of the maximum possible number of T cells for the amount of IL-7 available.