Human NK cell IFN-gamma production is regulated by endogenous TGF-beta

International Immunopharmacology
Sarah K MeadowsCharles L Sentman

Abstract

NK cells are an important component of innate immunity, and they can promote CTL and Th1 cell development and macrophage activation via cytokines. TGF-beta is believed to be an important immunoregulatory molecule, and for this reason several TGF-beta inhibitors are currently in clinical development. However, the modulation of specific innate immune responses by endogenous human TGF-beta remains unclear. In this study, we demonstrate that blocking the action of endogenous TGF-beta resulted in an increase in both the percentage of responding NK cells and the amount of IFN-gamma produced by human NK cells when stimulated by monokines and TLR agonists. Blocking endogenous TGF-beta resulted in significant NK cell IFN-gamma production under suboptimal stimulation conditions. Our findings also suggest that TGF-beta associated with other blood cells may be involved in limiting NK cell activation. Thus, inhibiting endogenous TGF-beta provides a means to shift NK cell activation and promote cellular immunity.

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Citations

Mar 10, 2007·The British Journal of Ophthalmology·Marta E PolakIan A Cree
Aug 16, 2013·The Journal of Clinical Investigation·Martin A IvarssonJakob Michaëlsson
Nov 10, 2012·The Journal of Reproduction and Development·Yurika TachibanaKazuhiko Imakawa
Dec 24, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ning LiBeinan Wang
Apr 13, 2007·The Journal of Investigative Dermatology·Minna AnthoniHarri T Alenius
Nov 2, 2006·American Journal of Reproductive Immunology : AJRI·Mikael ErikssonCharles L Sentman
Jan 16, 2007·American Journal of Reproductive Immunology : AJRI·Charles L SentmanMikael Eriksson
May 4, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vanessa Zaiatz-BittencourtClair M Gardiner
Sep 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rossana TrottaMichael A Caligiuri

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