The cellular amount of the common γ-chain influences spontaneous or induced cell proliferation

Stefania Amorosi, Ilaria Russo, Giada Amodio, Corrado Garbi, Laura Vitiello, Loredana Palamaro, Marsilio Adriani, Ilaria Vigliano, Claudio Pignata

Research output: Contribution to journalArticlepeer-review

Abstract

Mutations of the IL2RG encoding the common γ-chain (γc) lead to the X-linked SCID disease. Gene correction through ex vivo retroviral transduction restored the immunological impairment in the most of treated patients, although lymphoproliferative events occurred in five of them. Even though in two cases it was clearly documented an insertional mutagenesis in LMO2, it is conceivable that γc could have a role per se in malignant lymphoproliferation. The γc is a shared cytokine receptor subunit, involved also in growth hormone (GH) receptor signaling. Through short interfering RNA or using X-linked SCID B lympho-blastoid cell lines lacking γc, we demonstrate that self-sufficient growth was strongly dependent on γc expression. Furthermore, a correlation between γc amount and the extent of constitutive activation of JAK3 was found. The reduction of γc protein expression also reduced GH-induced proliferation and STAT5 nuclear translocation in B lymphoblastoid cell lines. Hence, our data demonstrate that γc plays a remarkable role in either spontaneous or GH-induced cell cycle progression depending on the amount of protein expression, suggesting a potential role as enhancing cofactor in lymphoproliferation.

Original languageEnglish
Pages (from-to)3304-3309
Number of pages6
JournalJournal of Immunology
Volume182
Issue number5
DOIs
Publication statusPublished - Mar 1 2009

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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