دورية أكاديمية
DOCK8 enforces immunological tolerance by promoting IL-2 signaling and immune synapse formation in Tregs.
| العنوان: | DOCK8 enforces immunological tolerance by promoting IL-2 signaling and immune synapse formation in Tregs. |
|---|---|
| المؤلفون: | Janssen E; Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA., Kumari S; Department of Bioengineering and Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA., Tohme M; Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA., Ullas S; Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA., Barrera V; Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Tas JM; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA., Castillo-Rama M; Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA., Bronson RT; Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA., Usmani SM; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA., Irvine DJ; Department of Bioengineering and Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA., Mempel TR; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA., Geha RS; Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA. |
| المصدر: | JCI insight [JCI Insight] 2017 Oct 05; Vol. 2 (19). Date of Electronic Publication: 2017 Oct 05. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight |
| أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
| مواضيع طبية MeSH: | Guanine Nucleotide Exchange Factors/*immunology , Immune Tolerance/*immunology , Immunological Synapses/*immunology , Interleukin-2/*immunology , T-Lymphocytes, Regulatory/*immunology, Animals ; Autoantibodies/biosynthesis ; Autoimmunity/immunology ; CD4-Positive T-Lymphocytes/immunology ; Gastroenteritis/immunology ; Guanine Nucleotide Exchange Factors/deficiency ; Inflammation/immunology ; Lymph Nodes/immunology ; Mice, Knockout ; Phosphorylation/immunology ; STAT5 Transcription Factor/metabolism ; Weight Gain/immunology |
| مستخلص: | Patients deficient in the guanine nucleotide exchange factor DOCK8 have decreased numbers and impaired in vitro function of Tregs and make autoantibodies, but they seldom develop autoimmunity. We show that, similarly, Dock8-/- mice have decreased numbers and impaired in vitro function of Tregs but do not develop autoimmunity. In contrast, mice with selective DOCK8 deficiency in Tregs develop lymphoproliferation, autoantibodies, and gastrointestinal inflammation, despite a normal percentage and in vitro function of Tregs, suggesting that deficient T effector cell function might protect DOCK8-deficient patients from autoimmunity. We demonstrate that DOCK8 associates with STAT5 and is important for IL-2-driven STAT5 phosphorylation in Tregs. DOCK8 localizes within the lamellar actin ring of the Treg immune synapse (IS). Dock8-/- Tregs have abnormal TCR-driven actin dynamics, decreased adhesiveness, an altered gene expression profile, an unstable IS with decreased recruitment of signaling molecules, and impaired transendocytosis of the costimulatory molecule CD86. These data suggest that DOCK8 enforces immunological tolerance by promoting IL-2 signaling, TCR-driven actin dynamics, and the IS in Tregs. |
| References: | Curr Top Microbiol Immunol. 2015;388:21-37. (PMID: 25553793) J Immunol. 2017 Apr 1;198(7):2612-2625. (PMID: 28228556) Nature. 2015 Dec 10;528(7581):225-30. (PMID: 26605524) Curr Opin Allergy Clin Immunol. 2010 Dec;10(6):515-20. (PMID: 20864884) Science. 2015 Aug 28;349(6251):989-93. (PMID: 26160380) J Exp Med. 2011 Sep 26;208(10):2055-67. (PMID: 21893603) PLoS One. 2012;7(9):e44328. (PMID: 22957064) J Immunol. 1999 May 1;162(9):5078-84. (PMID: 10227976) Nat Protoc. 2014 Jan;9(1):171-81. (PMID: 24385147) Biol Direct. 2008 Feb 27;3:6. (PMID: 18304352) Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3909-13. (PMID: 9108078) Eur J Immunol. 2011 Dec;41(12):3423-35. (PMID: 21969276) Am J Pathol. 1987 Feb;126(2):303-14. (PMID: 3826296) J Immunol. 2015 Mar 1;194(5):2148-59. (PMID: 25632005) Semin Immunopathol. 2017 Feb;39(2):153-163. (PMID: 27456849) Immunol Rev. 2008 Feb;221:77-89. (PMID: 18275476) BMC Genomics. 2017 Apr 18;18(1):305. (PMID: 28420336) Immunity. 2010 Aug 27;33(2):153-65. (PMID: 20732639) Nature. 2013 Sep 12;501(7466):252-6. (PMID: 23913274) N Engl J Med. 2009 Nov 19;361(21):2046-55. (PMID: 19776401) J Cell Sci. 2005 Nov 1;118(Pt 21):4937-46. (PMID: 16254241) Biochem Biophys Res Commun. 2010 Jan 1;391(1):159-65. (PMID: 19903453) Clin Immunol. 2012 Jun;143(3):266-72. (PMID: 22534316) Nat Commun. 2017 Mar 14;8:14649. (PMID: 28290453) J Immunol. 2012 Mar 15;188(6):2712-21. (PMID: 22312127) J Clin Invest. 2016 Oct 3;126(10):3837-3851. (PMID: 27599296) Nat Immunol. 2014 May;15(5):473-81. (PMID: 24633226) Elife. 2015 Mar 11;4:. (PMID: 25758716) Clin Exp Immunol. 2007 Jan;147(1):60-70. (PMID: 17177964) Nat Methods. 2013 Nov;10(11):1096-8. (PMID: 24056875) Am J Physiol Gastrointest Liver Physiol. 2016 Jun 1;310(11):G973-88. (PMID: 27079612) J Allergy Clin Immunol. 2009 Dec;124(6):1289-302.e4. (PMID: 20004785) Curr Protoc Mol Biol. 2014 Jul 01;107:4.22.1-17. (PMID: 24984854) J Cell Sci. 2007 Mar 1;120(Pt 5):723-30. (PMID: 17314246) Nature. 1999 Nov 18;402(6759):255-62. (PMID: 10580495) Immunity. 2014 Apr 17;40(4):569-81. (PMID: 24745333) Immunol Rev. 2016 May;271(1):141-55. (PMID: 27088912) J Exp Med. 2013 Mar 11;210(3):475-89. (PMID: 23460729) Cell. 2008 May 30;133(5):775-87. (PMID: 18510923) J Invest Dermatol. 2015 Dec;135(12):2982-2991. (PMID: 26203637) Nat Immunol. 2009 Dec;10(12):1283-91. (PMID: 19898472) Immunology. 2005 Jun;115(2):179-88. (PMID: 15885123) J Exp Med. 2011 Oct 24;208(11):2305-20. (PMID: 22006977) J Immunol. 2014 Dec 15;193(12):5894-903. (PMID: 25355918) World J Gastroenterol. 2016 Feb 21;22(7):2195-205. (PMID: 26900284) Nat Rev Immunol. 2016 Apr;16(4):220-33. (PMID: 27026074) J Allergy Clin Immunol. 2015 Aug;136(2):402-12. (PMID: 25724123) Nat Immunol. 2015 Feb;16(2):197-206. (PMID: 25501630) Nat Immunol. 2014 Aug;15(8):767-76. (PMID: 24973820) Genome Biol. 2003;4(9):117. (PMID: 12952525) Infect Immun. 2014 Jun;82(6):2239-46. (PMID: 24643531) J Immunol. 1982 Aug;129(2):665-72. (PMID: 6806378) Mol Biosyst. 2009 Dec;5(12):1512-26. (PMID: 20023718) Nat Immunol. 2014 Nov;15(11):1070-8. (PMID: 25263123) J Allergy Clin Immunol. 2013 Mar;131(3):840-8. (PMID: 23380217) J Clin Immunol. 2013 Jan;33(1):55-67. (PMID: 22968740) PLoS One. 2013 Aug 21;8(8):e69378. (PMID: 23990882) Trends Cell Biol. 2007 Aug;17(8):383-93. (PMID: 17765544) J Clin Invest. 2015 Nov 2;125(11):4053-62. (PMID: 26413872) J Immunol. 2013 Mar 15;190(6):2614-21. (PMID: 23390295) J Allergy Clin Immunol. 2014 Dec;134(6):1365-1374. (PMID: 25218284) J Immunol. 2004 Jun 1;172(11):6519-23. (PMID: 15153463) Cell. 2006 Dec 1;127(5):1015-26. (PMID: 17129785) J Exp Med. 2010 Aug 30;207(9):1871-8. (PMID: 20679400) Immunol Rev. 2010 Jul;236:219-42. (PMID: 20636820) Front Immunol. 2012 Aug 17;3:230. (PMID: 22912631) Exp Cell Res. 2016 Jan 1;340(1):132-8. (PMID: 26683997) Eur J Immunol. 2014 Jun;44(6):1633-43. (PMID: 24700244) Int J Clin Exp Pathol. 2014 Jul 15;7(8):4557-76. (PMID: 25197329) J Exp Med. 2014 Dec 15;211(13):2549-66. (PMID: 25422492) Cytoskeleton (Hoboken). 2013 Jul;70(7):360-84. (PMID: 23749648) Blood. 2012 May 10;119(19):4451-61. (PMID: 22461490) Gastroenterology. 1991 Aug;101(2):287-94. (PMID: 1648525) J Exp Med. 2002 Jul 15;196(2):255-60. (PMID: 12119350) Genes Immun. 2014 Dec;15(8):511-20. (PMID: 25056447) J Immunol. 2013 Apr 1;190(7):3661-9. (PMID: 23455509) Blood. 2007 May 15;109(10):4368-75. (PMID: 17227828) PLoS One. 2014 Jan 13;9(1):e85090. (PMID: 24454796) J Clin Immunol. 2012 Aug;32(4):698-708. (PMID: 22476911) Blood. 2012 May 10;119(19):4430-40. (PMID: 22438251) Science. 2011 Apr 29;332(6029):600-3. (PMID: 21474713) PLoS One. 2014 Oct 03;9(10):e109194. (PMID: 25279717) Immunol Cell Biol. 2016 Nov;94(10):981-993. (PMID: 27359298) Ann N Y Acad Sci. 2018 Apr;1417(1):5-22. (PMID: 26918796) Immunity. 2009 Jun 19;30(6):899-911. (PMID: 19464196) Am J Gastroenterol. 1999 Oct;94(10):2923-8. (PMID: 10520846) |
| معلومات مُعتمدة: | K08 AI114968 United States AI NIAID NIH HHS; P01 AI078897 United States AI NIAID NIH HHS; P30 DK043351 United States DK NIDDK NIH HHS |
| المشرفين على المادة: | 0 (Autoantibodies) 0 (Dock8 protein, mouse) 0 (Guanine Nucleotide Exchange Factors) 0 (Interleukin-2) 0 (STAT5 Transcription Factor) |
| تواريخ الأحداث: | Date Created: 20171006 Date Completed: 20190729 Latest Revision: 20200306 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC5841868 |
| DOI: | 10.1172/jci.insight.94298 |
| PMID: | 28978806 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2379-3708 |
|---|---|
| DOI: | 10.1172/jci.insight.94298 |