Orchestrating Lymphocyte Polarity in Cognate Immune Cell-Cell Interactions.
The immune synapse (IS) is a specialized structure established between different immune cells that fulfills several functions, including a role as a communication bridge. This intimate contact between a T cell and an antigen-presenting cell promotes the proliferation and differentiation of lymphocytes involved in the contact. T-cell activation requires the specific triggering of the T-cell receptor (TCR), which promotes the activation of different signaling pathways inducing the polarization of the T cell. During this process, different adhesion and signaling receptors reorganize at specialized membrane domains, concomitantly to the polarization of the tubulin and actin cytoskeletons, forming stable polarization platforms. The centrosome also moves toward the IS, driving the movement of different organelles, such as the biosynthetic, secretory, degrading machinery, and mitochondria, to sustain T-cell activation. A proper orchestration of all these events is essential for T-cell effector functions and the accomplishment of a complete immune response.
Vascular Pathophysiology Area, Spanish National Center of Cardiovascular Research (CNIC), Madrid, Spain.
Eugenio
E
Bustos-Morán
Department of Immunology, La Princesa Hospital, Autonomus University of Madrid (UAM), Health Research Institute of Princesa Hospital (ISS-IP), Madrid, Spain.
Noelia
N
Blas-Rus
Vascular Pathophysiology Area, Spanish National Center of Cardiovascular Research (CNIC), Madrid, Spain.|Department of Immunology, La Princesa Hospital, Autonomus University of Madrid (UAM), Health Research Institute of Princesa Hospital (ISS-IP), Madrid, Spain.
Noa Beatriz
NB
Martín-Cófreces
Vascular Pathophysiology Area, Spanish National Center of Cardiovascular Research (CNIC), Madrid, Spain.|Department of Immunology, La Princesa Hospital, Autonomus University of Madrid (UAM), Health Research Institute of Princesa Hospital (ISS-IP), Madrid, Spain.
Francisco
F
Sánchez-Madrid
D000818:Animals; D002450:Cell Communication / Q000276:immunology*; D016764:Cell Polarity / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000166:cytology*; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology*; D021962:Membrane Microdomains / Q000378:metabolism; D015388:Organelles / Q000378:metabolism
T-cell receptor; asymmetric cell division; centrosome; cytoskeleton; exosome; immune synapse; mitochondria; signaling
Nat Immunol. 2014 May;15(5):465-72
24705298
J Cell Biol. 2013 Jul 8;202(1):15-23
23836927
J Cell Sci. 2011 Aug 1;124(Pt 15):2539-51
21768326
Annu Rev Cell Dev Biol. 2010;26:421-44
20507227
J Cell Biol. 2006 Mar 13;172(6):923-35
16533950
Am J Physiol Endocrinol Metab. 2010 Mar;298(3):E395-402
19934406
Am J Hum Genet. 2009 Oct;85(4):482-92
19804848
J Immunol. 2010 Nov 1;185(9):5268-78
20881190
J Immunol. 2015 Mar 1;194(5):2249-59
25617472
Blood. 2007 Sep 15;110(6):1906-15
17525286
Immunity. 2010 Apr 23;32(4):531-40
20399684
Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2587-91
8146159
J Immunol. 2001 Dec 15;167(12):6736-44
11739488
Trends Cell Biol. 2014 Oct;24(10 ):564-74
24953741
Cold Spring Harb Perspect Biol. 2013 Feb 01;5(2):null
23378591
J Immunol. 2009 Apr 1;182(7):4046-55
19299702
Immunol Rev. 2010 May;235(1):10-23
20536552
Nat Commun. 2016 Apr 19;7:11389
27091106
Curr Opin Cell Biol. 2015 Aug;35:91-7
25988547
J Cell Sci. 2000 Oct;113 Pt 19:3365-74
10984428
Nature. 2015 May 28;521(7553):529-32
25945738
Trends Cell Biol. 2014 Dec;24(12):761-70
25189346
Nat Rev Mol Cell Biol. 2012 Oct;13(10):607-25
22992592
Nat Immunol. 2011 Jul 24;12(9):861-9
21785411
J Exp Med. 2013 Oct 21;210(11):2415-33
24101378
J Cell Sci. 1998 Jan;111 ( Pt 1):1-9
9394007
Trends Cell Biol. 2014 Sep;24(9):537-45
24786308
J Biol Chem. 1997 Dec 5;272(49):30889-98
9388235
EMBO J. 2011 Aug 16;30(19):3895-912
21847095
Immunology. 2008 Sep;125(1):70-9
18397268
Immunity. 1996 Jun;4(6):535-43
8673700
Immunol Rev. 2002 Nov;189:123-35
12445270
Mol Immunol. 2011 Jan;48(4):592-9
21112091
PLoS One. 2014 Mar 14;9(3):e91926
24632942
J Immunol. 2011 Sep 1;187(5):2233-43
21788445
Immunity. 2015 Oct 20;43(4):776-87
26384546
Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):17099-104
21949383
PLoS Pathog. 2011 Oct;7(10):e1002316
22046129
Nat Rev Immunol. 2011 Mar;11(3):201-12
21331080
Nat Genet. 2000 Jun;25(2):173-6
10835631
EMBO J. 2011 Apr 6;30(7):1238-50
21326213
Immunity. 2012 Oct 19;37(4):709-20
23084359
Curr Opin Immunol. 2002 Feb;14(1):66-74
11790534
Nat Immunol. 2006 Aug;7(8):803-9
16855606
Nat Cell Biol. 2013 Jul;15(7):741-50
23685627
J Cell Sci. 2014 May 1;127(Pt 9):1924-37
24554435
Nat Cell Biol. 2007 Jun;9(6):654-9
17486113
Cell. 2002 Jun 28;109(7):901-12
12110186
Trends Cell Biol. 2014 Jan;24(1):61-72
24119664
J Cell Sci. 2015 Jul 15;128(14 ):2541-52
26034069
J Cell Biol. 2001 Feb 19;152(4):825-34
11266472
Front Immunol. 2016 Jan 11;6:653
26793193
Cell. 2008 Feb 22;132(4):583-97
18295577
Nat Immunol. 2007 Mar;8(3):257-67
17237785
Immunity. 2015 May 19;42(5):864-76
25992860
Sci Signal. 2012 Apr 24;5(221):rs3
22534133
Cell Metab. 2015 Sep 1;22(3):485-98
26299452
Immunol Rev. 2013 Nov;256(1):118-32
24117817
Virol J. 2011 Oct 25;8:479
22023811
J Exp Med. 2004 Apr 5;199(7):981-91
15067034
J Cell Sci. 2011 Mar 1;124(Pt 5):820-30
21321329
PLoS One. 2012;7(2):e31156
22347445
J Extracell Vesicles. 2015 May 14;4:27066
25979354
Blood. 2000 May 15;95(10):3199-203
10807788
Nat Rev Immunol. 2009 Sep;9(9):662-8
19680250
Curr Biol. 2009 Dec 1;19(22):1875-85
19896381
Nat Rev Mol Cell Biol. 2014 Oct;15(10):634-46
25237825
Immunity. 2010 Oct 29;33(4):607-19
20888269
Autophagy. 2012 Nov;8(11):1690-2
22874554
Biochemistry. 2009 Mar 10;48(9):2045-52
19152501
Curr Opin Cell Biol. 2003 Jun;15(3):338-44
12787777
Nat Immunol. 2009 May;10(5):531-9
19349987
EMBO J. 2009 Apr 22;28(8):1016-28
19242490
Science. 2012 Jan 20;335(6066):342-4
22174128
Sci Signal. 2014 Oct 21;7(348):ra99
25336615
Cold Spring Harb Symp Quant Biol. 2008;73:73-9
19022740
Immunol Rev. 2002 Aug;186:68-82
12234363
EMBO Rep. 2008 Jun;9(6):525-30
18516087
Front Immunol. 2011 Dec 07;2:72
22566861
J Biol Chem. 2014 Sep 12;289(37):25936-45
25070895
J Cell Sci. 1998 Oct;111 ( Pt 20):3081-90
9739081
Mol Biol Cell. 2007 Sep;18(9):3250-63
17567948
J Cell Biol. 2010 Jun 14;189(6):997-1011
20548102
Nat Immunol. 2009 Jun;10(6):627-35
19430478
Immunity. 2009 Oct 16;31(4):621-31
19833087
Nat Cell Biol. 2009 Nov;11(11):1332-9
19855387
J Mol Biol. 2002 Sep 27;322(4):785-97
12270714
FASEB J. 2006 Apr;20(6):711-3
16452278
Blood. 2013 Apr 4;121(14):2659-68
23377437
Cell. 2013 Jan 17;152(1-2):290-303
23332761
Immunity. 2006 Jun;24(6):753-65
16782031
Cytokine. 2001 Apr 21;14(2):63-77
11356007
Nat Rev Immunol. 2005 Jul;5(7):532-45
15999094
J Leukoc Biol. 2010 Mar;87(3):425-32
19892849
Biochim Biophys Acta. 2015 Apr;1853(4):802-9
25535948
Mol Biol Cell. 2006 Aug;17(8):3435-45
16738306
Blood. 2009 Nov 5;114(19):4117-27
19704116
Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):11058-63
15263094
J Cell Sci. 1993 Jan;104 ( Pt 1):151-62
8449993
Mol Cell Biol. 2013 Sep;33(18):3644-58
23858057
Cell Death Differ. 2011 Jul;18(7):1161-73
21252909
Nat Immunol. 2006 Mar;7(3):247-55
16444260
Mol Cell Biol. 2014 Apr;34(8):1486-99
24515439
Nat Immunol. 2005 Mar;6(3):261-70
15696170
Curr Opin Immunol. 2007 Jun;19(3):301-8
17433871
Nature. 2003 Apr 17;422(6933):766-74
12700771
Immunity. 2010 Aug 27;33(2):153-65
20732639
Nat Rev Immunol. 2003 Apr;3(4):269-79
12669018
Exp Cell Res. 2001 Nov 15;271(1):10-21
11697877
Traffic. 2015 Mar;16(3):241-9
25393976
Mol Biol Cell. 2004 Jun;15(6):2932-42
15064353
Curr Opin Cell Biol. 2008 Feb;20(1):4-11
18222686
Annu Rev Biochem. 2012;81:167-76
22663079
J Biol Chem. 2003 Dec 26;278(52):52347-54
14561735
J Cell Sci. 2004 Mar 1;117(Pt 7):1009-16
14996932
Cold Spring Harb Perspect Biol. 2010 Aug;2(8):a005512
20610546
EMBO J. 2010 Dec 1;29(23):4035-47
20953162
Nat Commun. 2011;2:282
21505438
Trends Cell Biol. 2009 Sep;19(9):434-46
19709882
Mol Biol Cell. 2013 Mar;24(5):643-58
23283983
Annu Rev Biochem. 2011;80:613-43
21495847
Immunity. 1998 Aug;9(2):239-46
9729044
J Immunol. 2012 Sep 1;189(5):2159-68
22821962
Immunol Rev. 2013 Jan;251(1):125-42
23278745
Neuron. 2009 Feb 26;61(4):541-55
19249275
Hum Mutat. 2006 Jan;27(1):62-8
16278825
J Immunol. 2010 Sep 1;185(5):2887-94
20679531
Immunity. 2009 Oct 16;31(4):632-42
19833088
Trends Cell Biol. 2005 Dec;15(12 ):644-50
16260137
Immunol Rev. 2013 Nov;256(1):95-106
24117815
Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):378-83
19966284
J Cell Biol. 2010 May 17;189(4):671-9
20457763
Cell Death Differ. 2013 Feb;20(2):188-97
23175183
Traffic. 2015 Feb;16(2):191-203
25425525
J Cell Biol. 2006 May 22;173(4):545-57
16717129
Cell. 2013 Sep 12;154(6):1285-99
24034251
J Cell Sci. 2013 Dec 15;126(Pt 24):5553-65
24105262
Blood. 2010 Dec 23;116(26):5919-29
20881207
Virol J. 2010 Sep 16;7:234
20846372
Semin Cancer Biol. 2014 Oct;28:3-13
24769058
Nat Cell Biol. 2011 Feb;13(2):132-41
21258367
Nat Cell Biol. 2010 Sep;12(9):831-5
20811355
Nature. 2014 Mar 6;507(7490):118-23
24487619
Immunity. 2008 May;28(5):698-709
18450485
Nat Immunol. 2011 May 22;12(7):647-54
21602810
J Immunol. 2004 Mar 15;172(6):3527-34
15004153
Biochem J. 2012 Mar 15;442(3):649-59
22233340
Nat Rev Immunol. 2013 Sep;13(9):666-78
23907446
Nat Immunol. 2002 Dec;3(12 ):1192-9
12415267
J Biol Chem. 2004 Dec 31;279(53):55376-84
15516342
Blood. 2012 Apr 26;119(17 ):3879-89
22308290
Mol Immunol. 2005 Feb;42(3):305-10
15589318
Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10592-7
12947040
Biochem J. 2012 Jan 15;441(2):553-69
22187936
Nat Rev Immunol. 2010 Aug;10(8):568-79
20634814
Nature. 1997 Jun 5;387(6633):569-72
9177342
Nat Commun. 2013;4:2980
24356509
Curr Opin Cell Biol. 2004 Jun;16(3):223-9
15145345
Nat Immunol. 2010 Jan;11(1):90-6
20010844
Nat Immunol. 2008 Oct;9(10):1105-11
18800163
J Biol Chem. 2003 Feb 21;278(8):6495-502
12482879
Front Immunol. 2011 Jul 04;2:24
22566814
J Cell Sci. 2005 Jun 15;118(Pt 12):2579-87
15928049
Trends Cell Biol. 2014 Oct;24(10):584-93
24841758
Mol Biol Cell. 2010 Jul 1;21(13):2241-56
20444980
Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3909-13
9108078
Immunity. 2011 Sep 23;35(3):375-87
21903423
Trends Cell Biol. 2014 Jan;24(1):73-81
23999079
J Cell Biol. 2011 Nov 28;195(5):781-97
22123863
Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11976-81
23818610
J Cell Biol. 2013 Aug 5;202(3):527-43
23897888
Nat Commun. 2016 Mar 18;7:10969
26987298
Nat Rev Mol Cell Biol. 2009 Sep;10(9):623-35
19672277
Nat Cell Biol. 2011 Dec 22;14(1):20-8
22193160
Immunity. 2011 Aug 26;35(2):208-22
21820331
Nat Rev Mol Cell Biol. 2011 Jan;12(1):9-14
21179058
Blood. 2010 May 27;115(21):4174-84
20231423
J Cell Sci. 2004 Oct 15;117(Pt 22):5343-51
15466889
Immunol Lett. 2009 Jan 29;122(1):18-25
19038287
Nat Immunol. 2014 Sep;15(9):808-14
25137455
Cold Spring Harb Perspect Biol. 2010 Oct;2(10):a002311
20843980
Nat Immunol. 2013 Jul;14(7):723-31
23666293
J Cell Biol. 2011 Feb 21;192(4):663-74
21339332
Mol Biol Cell. 2014 May;25(10 ):1629-40
24648492
J Immunol. 2012 May 1;188(9):4145-8
22467651
Crit Rev Immunol. 2013;33(5):435-76
24099302
J Immunol. 2011 Sep 15;187(6):2993-3002
21849673
J Immunol. 2011 Sep 15;187(6):3362-73
21849676
Trends Immunol. 2015 Nov;36(11):670-83
26474675
Science. 2005 Nov 18;310(5751):1159-63
16293754
Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10507-12
18641128
Curr Opin Cell Biol. 2015 Aug;35:117-22
26022676
Mol Biol Cell. 2004 Jun;15(6):2771-81
15047863
J Immunol. 2007 Oct 15;179(8):5301-8
17911616
Science. 2005 Nov 18;310(5751):1191-3
16293763
Eur J Immunol. 2014 Jul;44(7):1967-75
24723389
Immunity. 2007 Feb;26(2):177-90
17306570
Immunol Rev. 2009 Sep;231(1):132-47
19754894
Cold Spring Harb Perspect Biol. 2012 Nov 01;4(11):null
23125018
J Immunol. 2015 Jun 1;194(11):5509-19
25917087
Blood. 2006 Oct 1;108(7):2316-23
16778144
Mol Cell Biol. 1994 Aug;14(8):5384-91
8035816
J Cell Sci. 2016 Apr 1;129(7):1305-11
26869226
Blood. 2016 Apr 14;127(15):1930-9
26837700
Science. 2011 Apr 29;332(6029):600-3
21474713
Sci Signal. 2010 May 11;3(121):ra36
20460647
Protein Cell. 2011 Feb;2(2):150-60
21359602
J Immunol. 2002 May 1;168(9):4420-9
11970985
Trends Cell Biol. 2014 Jan;24(1):9-18
24076263
Traffic. 2011 Dec;12(12):1659-68
21645191
Hum Mol Genet. 2005 Apr 15;14(8):1077-86
15772097
Biochim Biophys Acta. 2014 Jun;1838(6):1451-66
24189436
J Clin Invest. 2009 Dec;119(12):3765-73
19884660
Cell Death Differ. 2016 Jan;23 (1):99-109
26045048
Immunity. 2004 May;20(5):577-88
15142526
Blood. 2011 Nov 17;118(20):5487-97
21972292
Nat Immunol. 2014 Dec;15(12):1152-61
25362489
Mol Cell Biol. 2014 Apr;34(8):1412-26
24492963
Immunity. 2004 Apr;20(4):417-28
15084271
Nat Immunol. 2003 Jul;4(7):670-9
12796776
Nature. 2006 Sep 28;443(7110):462-5
17006514
Nat Commun. 2015 Jun 17;6:7474
26081938
J Exp Med. 2008 Dec 22;205(13):3201-13
19064697
J Immunol. 2004 Jun 1;172(11):6709-14
15153487
Nat Rev Mol Cell Biol. 2009 May;10 (5):360-4
19293819
Immunity. 2006 Jul;25(1):117-27
16860761
EMBO J. 2012 Nov 5;31(21):4140-52
22922463
Science. 2003 Nov 14;302(5648):1218-22
14512504
Nephrol Dial Transplant. 2013 Nov;28(11):2744-53
24026243
Sci Signal. 2014 Apr 22;7(322):ra37
24757177
J Biol Chem. 1997 Dec 5;272(49):30848-51
9388229
Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14883-8
16990435
Proc Natl Acad Sci U S A. 2012 Mar 13;109 (11):4146-51
22315426
Curr Biol. 2014 Mar 17;24(6):609-20
24613307
Physiology (Bethesda). 2010 Apr;25(2):102-15
20430954
J Cell Biol. 1991 Dec;115(6):1505-19
1757460
J Immunol. 2010 Jul 1;185(1):367-75
20530266
Nature. 1998 Sep 3;395(6697):82-6
9738502
Cell Cycle. 2012 Jun 15;11(12):2219-20
22617383
Immunity. 2011 Jun 24;34(6):919-31
21703543
J Immunol. 2012 Jun 1;188(11):5421-7
22529300
PLoS One. 2009 Dec 22;4(12):e8290
20027317
Cell. 1991 Nov 1;67(3):601-16
1682055
EMBO J. 2014 Mar 18;33(6):559-77
24502978
J Cell Biol. 1998 Jan 26;140(2):259-70
9442102
Immunity. 2010 Sep 24;33(3):326-39
20870175
PLoS Genet. 2012;8(3):e1002537
22396657
J Cell Biol. 2003 Aug 4;162(3):435-42
12900395
J Immunol. 2006 Apr 1;176(7):4201-7
16547257
J Immunol. 2011 Jun 1;186(11):6345-56
21508261
Immunol Rev. 2008 Aug;224:249-64
18759932
Mol Cell. 2015 Sep 3;59(5):840-9
26321253
Mol Biol Cell. 2009 Feb;20(4):1192-200
19109421
Immunity. 2013 Apr 18;38(4):633-43
23601682
Annu Rev Cell Dev Biol. 2007;23:495-517
17506701
J Cell Biol. 2010 Aug 9;190(3):347-61
20696705
Nat Rev Immunol. 2004 Feb;4(2):110-22
15040584
Nat Immunol. 2012 Jul 01;13(8):787-95
22751140
Int J Mol Sci. 2013 Mar 26;14(4):6649-73
23531532
J Cell Biol. 2012 Sep 17;198(6):1025-37
22986496
Curr Opin Cell Biol. 2009 Apr;21(2):262-7
19195860
Mol Biol Cell. 2008 May;19(5):2300-10
18305100
Science. 2007 Mar 23;315(5819):1687-91
17332376
PLoS One. 2014 Jan 27;9(1):e87376
24475281
Nature. 2005 Aug 4;436(7051):704-8
16079847
Cell. 2003 Nov 14;115(4):461-73
14622600
Curr Opin Cell Biol. 2016 Apr;39:8-14
26827287
Cell. 2014 Jul 3;158(1):54-68
24995978
Front Immunol. 2012 Jul 31;3:235
23060874
Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14418-23
17726106
J Cell Biol. 2008 Sep 8;182(5):951-62
18779373
Nat Rev Mol Cell Biol. 2012 Apr 18;13(5):328-35
22510790
J Immunol. 2006 Oct 15;177(8):5163-8
17015701
Nat Immunol. 2013 Nov;14(11):1155-65
24056747