Successful Regulatory T Cell-Based Therapy Relies on Inhibition of T Cell Effector Function and Enrichment of FOXP3+ Cells in a Humanized Mouse Model of Skin Inflammation.

Journal of Immunology Research
Sija LandmanHans J P M Koenen

Abstract

Recent clinical trials using regulatory T cells (Treg) support the therapeutic potential of Treg-based therapy in transplantation and autoinflammatory diseases. Despite these clinical successes, the effect of Treg on inflamed tissues, as well as their impact on immune effector function in vivo, is poorly understood. Therefore, we here evaluated the effect of human Treg injection on cutaneous inflammatory processes in vivo using a humanized mouse model of human skin inflammation (huPBL-SCID-huSkin). SCID beige mice were transplanted with human skin followed by intraperitoneal (IP) injection of 20-40 × 106 allogeneic human PBMCs. This typically results in human skin inflammation as indicated by epidermal thickening (hyperkeratosis) and changes in dermal inflammatory markers such as the antimicrobial peptide hBD2 and epidermal barrier cytokeratins K10 and K16, as well as T cell infiltration in the dermis. Ex vivo-expanded human Treg were infused intraperitoneally. Human cutaneous inflammation and systemic immune responses were analysed by immunohistochemistry and flow cytometry. We confirmed that human Treg injection inhibits skin inflammation and the influx of effector T cells. As a novel finding, we demonstrate that human Treg i...Continue Reading

References

Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·A G MurrayJ S Pober
Aug 30, 2001·Nature Immunology·K J Maloy, F Powrie
Dec 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hideaki SugiyamaKevin D Cooper
Mar 15, 2006·The Journal of Experimental Medicine·Alexander Y Rudensky, Daniel J Campbell
May 27, 2008·Journal of Autoimmunity·Valérie DardalhonAna C Anderson
Jun 20, 2008·Nature·Estelle BettelliVijay K Kuchroo
Jun 30, 2009·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Piotr TrzonkowskiAndrzej Hellmann
Jun 19, 2010·Nature Reviews. Immunology·Shimon SakaguchiDavid A Hafler
Jul 20, 2010·Immunotherapy·Jorieke H PetersIrma Joosten
Oct 1, 2010·Current Opinion in Organ Transplantation·Fadi Issa, Kathryn J Wood
Jun 10, 2011·The Journal of Investigative Dermatology·H Jorn BovenschenHans J P M Koenen
Jul 15, 2011·Current Opinion in Immunology·Fadi IssaKathryn J Wood
Jan 10, 2012·Annual Review of Immunology·Angelina M Bilate, Juan J Lafaille
Oct 13, 2012·Nature Reviews. Immunology·Leonard D ShultzDale L Greiner
Jul 3, 2013·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Piotr TrzonkowskiAndrzej Hellmann
Oct 10, 2013·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·A L PutnamQ Tang
Mar 25, 2014·Annual Review of Immunology·Michelle A LowesJames G Krueger
Apr 18, 2015·Expert Opinion on Therapeutic Targets·Jeffrey A BluestoneDaqi Xu
May 6, 2015·Current Transplantation Reports·Cecilia Cabello-KindelanAllison L Bayer
Nov 21, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·L L KenneyM A Brehm
Nov 27, 2015·Science Translational Medicine·Jeffrey A BluestoneQizhi Tang
Jan 17, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Satoru TodoKo Okumura
Jan 31, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sylvie GrégoireBenoît L Salomon
Dec 3, 2016·Journal of Translational Medicine·Natalia Marek-TrzonkowskaPiotr Trzonkowski
Dec 25, 2016·Transplant International : Official Journal of the European Society for Organ Transplantation·Marco RomanoGiovanna Lombardi

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Methods Mentioned

BETA
density gradient separation
PMA

Software Mentioned

ImageJ
GraphPad Prism
AxioVision

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