High dose CD11c-driven IL15 is sufficient to drive NK cell maturation and anti-tumor activity in a trans-presentation independent manner

Scientific Reports
Julia K PolanskySilvia Bulfone-Paus

Abstract

The common gamma (γc)-chain cytokine interleukin 15 (IL15) is a multifunctional immune-modulator which impacts the generation, maturation and activity of many cell types of the innate, as well as the adaptive immune system, including natural killer (NK) and CD8(+) T cells. Using a new series of transgenic mice, we analyzed the in vivo potential of IL15 as an immune-regulator when available at different concentrations or delivery modes, i.e. soluble monomer or complexed to its specific receptor α (Rα)-chain. We have identified distinct effects on selected IL15-responsive populations. While CD8(+) T cells required complexed forms of IL15/IL15Rα for full functionality, mature NK populations were rescued in an IL15/IL15Rα-deficient environment by high levels of CD11c-restricted IL15. These IL15-conditions were sufficient to limit tumor formation in a lung metastasis model indicating that the NK cell populations were fully functional. These data underline the potential of "free" IL15 in the absence of Rα-complex as a powerful and specific immuno-modulator, which may be beneficial where selective immune-activation is desired.

References

Jun 1, 1975·European Journal of Biochemistry·C Galanos, O Lüderitz
Mar 8, 2000·The Journal of Experimental Medicine·M K KennedyJ J Peschon
Jul 4, 2001·European Journal of Immunology·E E RosmarakiJ P Di Santo
Aug 21, 2001·Rheumatology·M AringerW B Graninger
Aug 30, 2001·Nature Immunology·F GranucciP Ricciardi-Castagnoli
Nov 16, 2002·Immunity·Sigrid DuboisYutaka Tagaya
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Thomas A StoklasekLeo Lefrançois
Apr 3, 2007·Immunity·Mathias LucasAndreas Diefenbach
Apr 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicholas D HuntingtonStephen L Nutt
Apr 7, 2007·Current Opinion in Rheumatology·Darren L Asquith, Iain B McInnes
Nov 6, 2007·Immunological Reviews·Claude GrégoireThierry Walzer
May 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Martin SchaeferTim Sparwasser
Sep 25, 2008·Blood·Spencer W StonierKimberly S Schluns
Feb 24, 2009·Blood·Laura ChiossoneThierry Walzer
Jun 26, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lisa J MaKimberly S Schluns
Sep 30, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eliseo F CastilloKimberly S Schluns
Jun 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chin-Ling ChangNan-Shih Liao
Jul 1, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gilbert Aaron LeeNan-Shih Liao
Nov 16, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura E GordySebastian Joyce
Mar 1, 2012·Cancer Research·Rebecca B LiuHans Schreiber
Jul 17, 2012·Cytokine·Eliseo F Castillo, Kimberly S Schluns
Aug 21, 2012·Nature Immunology·Natalie A BezmanUNKNOWN Immunological Genome Project Consortium
May 3, 2013·Proceedings of the National Academy of Sciences of the United States of America·Rebecca Berlant LiuBana Jabri
Nov 26, 2013·Frontiers in Immunology·Obinna Chijioke, Christian Münz
Jan 15, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Muriel MalaiséAlexander Kroemer
Jun 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Fella TamzalitErwan Mortier
Oct 31, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amy GillgrassAli A Ashkar
Nov 19, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kevin C ConlonThomas A Waldmann
Sep 26, 2015·Oncoimmunology·Rajia BahriSilvia Bulfone-Paus

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Citations

Mar 2, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Helen R WagstaffeMartin R Goodier
Jul 20, 2018·Nature Communications·Lele ZhuShao-Cong Sun
Nov 19, 2020·Journal for Immunotherapy of Cancer·Piera Filomena FioreBruno Azzarone

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Methods Mentioned

BETA
transgenic
ELISA
flow-cytometry
PCR
FCS
lavage
FACS
ELISAs

Software Mentioned

TreeStar
FlowJo7

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