The Common γ Chain (γc) Is a Required Signaling Component of the IL-21 Receptor and Supports IL-21-Induced Cell Proliferation via JAK3

• DOI: 10.1021/bi0202023
• Publication Date: 2002-07-28T21:28:27Z
• Authors: Tania Habib; Shantha Senadheera; Kenneth Weinberg; Kenneth Kaushansky
• Keywords: Common gamma chain

The common cytokine receptor γ chain (γc), an essential component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15, is critical development function lymphocytes. Recently, a novel lymphokine (IL-21) its (IL-21Rα) were described which profoundly affect growth activation state B, T, NK cells in concert with other lymphokines or stimuli [Parrish-Novak, J., et al. (2000) Nature 408, 57−63]. In this report, we show that γc also required signaling IL-21 (IL-21R) using γc-deficient X-linked severe combined immunodeficiency (XSCID) lymphoblastoid cell line JT, JT reconstituted (JT/γc). Moreover, demonstrate functional requirement both γc-associated Janus family tyrosine kinase 3 (JAK3) IL-21-induced proliferation pro-B-lymphoid engineered to express human IL-21Rα (BaF3/IL-21Rα). Retroviral-mediated transduction wild-type into XSCID restored IL-21R, as shown by phosphorylation JAK1 JAK3, downstream STAT5, JT/γc well BaF3/IL-21Rα primary splenic B cells. contrast, failed activate JAK-STAT pathway nonreconstituted Monoclonal antibodies specific effectively inhibited cells, supporting role molecule IL-21R complex. addition, JAK3 inhibitor WHI-P131 significantly reduced Taken together, these results definitively IL-21-mediated requires chain, indicate transducer γc-dependent survival and/or mitogenic signals induced cytokine.