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A dual requirement for IL-7 and IL-15 in iNKT cell development and survival

Friday, November 08, 2013 — Poster Session IV

2:00 p.m. – 4:00 p.m.

FAES Academic Center (Upper-Level Terrace)



* FARE Award Winner


  • J.Y. Park
  • H.R. Keller
  • J.H. Park


Invariant natural killer T (iNKT) cells are thymus-generated T lineage cells with shared phenotypic and functional characteristics of innate NK cells. All T lineage cells require cytokine signaling for their development and differentiation, and iNKT cells were proposed to be dependent on IL-15. In contrast to this prevailing view, we found that iNKT cells were dependent on IL-7 and not on IL-15. Specifically, IL-7 was critical for both the development and survival of iNKT cells as IL-7-deficient mice showed dramatically reduced iNKT cell numbers both in the thymus and spleen. Moreover, using a new in vivo model of peripheral IL-7 deficiency (K7 mice), we further confirmed that IL-7 is a survival factor for iNKT cells. Notably, IL-7 was also important for iNKT cell function, as in vivo iNKT activation by aGalCer injection into K7 mice resulted in blunted IL-4/IFNg production compared to WT mice. Mechanistically, we identified STAT5 as the transcriptional effector molecule downstream of IL-7 signaling that drives iNKT cell development. Collectively, these data provide an entirely new perspective on cytokine requirements for iNKT cell survival and function, and proposes a new role for IL-7 in iNKT cell biology.

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