MerTK is required for apoptotic cell-induced T cell tolerance

The Journal of Experimental Medicine
Mark A WalletRoland Tisch

Abstract

Self-antigens expressed by apoptotic cells (ACs) may become targets for autoimmunity. Tolerance to these antigens is partly established by an ill-defined capacity of ACs to inhibit antigen-presenting cells such as dendritic cells (DCs). We present evidence that the receptor tyrosine kinase Mer (MerTK) has a key role in mediating AC-induced inhibition of DC activation/maturation. Pretreatment of DCs prepared from nonobese diabetic (NOD) mice with AC blocked secretion of proinflammatory cytokines, up-regulation of costimulatory molecule expression, and T cell activation. The effect of ACs on DCs was dependent on Gas6, which is a MerTK ligand. NOD DCs lacking MerTK expression (NOD.MerTK(KD/KD)) were resistant to AC-induced inhibition. Notably, autoimmune diabetes was exacerbated in NOD.MerTK(KD/KD) versus NOD mice expressing the transgenic BDC T cell receptor. In addition, beta cell-specific CD4(+) T cells adoptively transferred into NOD.MerTK(KD/KD) mice in which beta cell apoptosis was induced with streptozotocin exhibited increased expansion and differentiation into type 1 T cell effectors. In both models, the lack of MerTK expression was associated with an increased frequency of activated pancreatic CD11c(+)CD8alpha(+) DCs, wh...Continue Reading

References

Oct 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·K HaskinsB Bradley
Jan 1, 1980·International Review of Cytology·A H WyllieA R Currie
Mar 1, 1993·Immunology Today·J SavillC Haslett
Dec 6, 1997·Nature·R E VollI Girkontaite
Jun 22, 1999·The Journal of Experimental Medicine·T OhtekiS Koyasu
Feb 9, 2000·The Journal of Experimental Medicine·R M SteinmanK Inaba
Mar 4, 2000·Human Molecular Genetics·P M D'CruzD Vollrath
Apr 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·H HochreinM O'Keeffe
May 11, 2001·Nature·R S ScottG K Matsushima
Nov 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·Y N NaumovS B Wilson
Jan 10, 2002·The Journal of Clinical Investigation·Mai-Lan N HuynhPeter M Henson
Feb 5, 2002·Experimental Eye Research·M O HallB J Agnew
May 22, 2002·The Journal of Experimental Medicine·Tomonori IyodaKayo Inaba
May 29, 2002·The Journal of Biological Chemistry·Mark M W ChongThomas W H Kay
Jul 3, 2002·The Journal of Experimental Medicine·Philip L CohenElizabeth A Reap
Jan 31, 2003·Investigative Ophthalmology & Visual Science·Jacque L DuncanDouglas Vollrath
Jun 10, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Michael F Reidy, Jo Rae Wright
Jul 29, 2003·European Journal of Immunology·Edward M BehrensPhilip L Cohen
Jun 8, 2004·Advances in Experimental Medicine and Biology·Jacque L DuncanMatthew M LaVail
Nov 6, 2004·Current Rheumatology Reports·Udo S GaiplMartin Herrmann
Mar 17, 2005·Physiological Genomics·Nancy C Jerez-TimaureDaniel Pomp
Sep 15, 2005·Clinical Medicine & Research·Mark A WalletRoland Tisch
Jan 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carmen P WongRoland Tisch
Mar 15, 2006·Trends in Cell Biology·Yi WuRaymond B Birge
Apr 1, 2006·International Immunology·Mark D McKenzieHelen E Thomas
Jun 30, 2006·Proceedings of the National Academy of Sciences of the United States of America·Petra SchnorrerJose A Villadangos
Jul 13, 2006·The Journal of Experimental Medicine·M Nusrat SharifLionel B Ivashkiv
Oct 13, 2006·Blood·H Franklin Bunn
Apr 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heather M SeitzGlenn K Matsushima

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Citations

Sep 28, 2010·Archivum Immunologiae Et Therapiae Experimentalis·Charles J KrogerRoland Tisch
Feb 9, 2010·Apoptosis : an International Journal on Programmed Cell Death·Adrian E Morelli, Adriana T Larregina
Jun 17, 2010·Apoptosis : an International Journal on Programmed Cell Death·Edward B Thorp
Aug 16, 2008·Immunologic Research·Barbara J Vilen, Jennifer A Rutan
Apr 19, 2008·Nature Reviews. Immunology·Greg Lemke, Carla V Rothlin
Sep 25, 2008·Nature Reviews. Molecular Cell Biology·Jason M Kinchen, Kodi S Ravichandran
Mar 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Mark A WalletRoland Tisch
Oct 21, 2010·The Journal of Biological Chemistry·Ceylan EkenJürg A Schifferli
Aug 22, 2012·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Iris J LeePhilip L Cohen
Sep 12, 2009·Journal of Gastroenterology and Hepatology·Soichiro UeharaMitiko Sennshuu
Dec 2, 2008·Pigment Cell & Melanoma Research·Sanaa El MarsafyAlain Mauviel
Jan 28, 2014·PloS One·Meredith J CraneJorge E Albina
May 9, 2013·Clinical & Developmental Immunology·Michael J GoughMarka Crittenden
Jan 15, 2014·Clinical Reviews in Allergy & Immunology·Annegret KuhnHeiko Weyd
Jan 22, 2013·Annual Review of Immunology·Gianna Elena Hammer, Averil Ma
Sep 25, 2014·The Journal of Clinical Investigation·Jamie C StanfordRebecca S Cook
Jun 13, 2012·Toxicology and Applied Pharmacology·Ye-Ji LeeJihee Lee Kang
Oct 30, 2010·Current Opinion in Immunology·Carla V Rothlin, Greg Lemke
Sep 9, 2010·Journal of Autoimmunity·Wen-Hai ShaoPhilip L Cohen
Jul 17, 2010·Trends in Parasitology·Ida M FribergJoseph A Jackson
Apr 21, 2010·Seminars in Immunology·Yuting MaLaurence Zitvogel
Jul 28, 2009·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Wen-Hai ShaoPhilip L Cohen
Jan 7, 2011·Immunology·Jim Hu, Yonghong Wan
Apr 15, 2011·Immunological Reviews·Santhakumar Manicassamy, Bali Pulendran
Dec 4, 2012·Arthritis and Rheumatism·B T van den BrandF A J van de Loo
Jul 25, 2009·Cellular Immunology·Julie C WilliamsGlenn K Matsushima
Aug 10, 2015·Journal of Autoimmunity·Juan Liu, Xuetao Cao
May 15, 2013·Autoimmunity·Khanh-Quynh NguyenRaymond B Birge
Mar 31, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Iris J LeePhilip L Cohen
Jan 17, 2015·Annual Review of Immunology·Carla V RothlinSourav Ghosh
Nov 13, 2013·Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis·Jeffrey S FutterleibRichard L Edelson
May 21, 2016·Proceedings of the National Academy of Sciences of the United States of America·Bishuang CaiIra Tabas

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Methods Mentioned

BETA
ELISA
FACS
transgenic
PCR
confocal microscopy

Software Mentioned

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