When the Damage Is Done: Injury and Repair in Thymus Function.
BMP4
IL-22
T cell reconstitution
endogenous thymic regeneration
immune restoration
thymic epithelial cells
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
29
04
2020
accepted:
30
06
2020
entrez:
9
9
2020
pubmed:
10
9
2020
medline:
13
4
2021
Statut:
epublish
Résumé
Even though the thymus is exquisitely sensitive to acute insults like infection, shock, or common cancer therapies such as cytoreductive chemo- or radiation-therapy, it also has a remarkable capacity for repair. This phenomenon of endogenous thymic regeneration has been known for longer even than its primary function to generate T cells, however, the underlying mechanisms controlling the process have been largely unstudied. Although there is likely continual thymic involution and regeneration in response to stress and infection in otherwise healthy people, acute and profound thymic damage such as that caused by common cancer cytoreductive therapies or the conditioning regimes as part of hematopoietic cell transplantation (HCT), leads to prolonged T cell deficiency; precipitating high morbidity and mortality from opportunistic infections and may even facilitate cancer relapse. Furthermore, this capacity for regeneration declines with age as a function of thymic involution; which even at steady state leads to reduced capacity to respond to new pathogens, vaccines, and immunotherapy. Consequently, there is a real clinical need for strategies that can boost thymic function and enhance T cell immunity. One approach to the development of such therapies is to exploit the processes of endogenous thymic regeneration into novel pharmacologic strategies to boost T cell reconstitution in clinical settings of immune depletion such as HCT. In this review, we will highlight recent work that has revealed the mechanisms by which the thymus is capable of repairing itself and how this knowledge is being used to develop novel therapies to boost immune function.
Identifiants
pubmed: 32903477
doi: 10.3389/fimmu.2020.01745
pmc: PMC7435010
doi:
Substances chimiques
Immunologic Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1745Subventions
Organisme : NIA NIH HHS
ID : P01 AG052359
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015704
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL145276
Pays : United States
Informations de copyright
Copyright © 2020 Kinsella and Dudakov.
Références
Blood. 2003 Jul 15;102(2):421-8
pubmed: 12663447
Annu Rev Immunol. 2010;28:343-65
pubmed: 20192807
Nature. 2006 Jun 22;441(7096):992-6
pubmed: 16791198
JCI Insight. 2019 May 7;5:
pubmed: 31063156
J Immunol. 2012 Nov 1;189(9):4451-8
pubmed: 23028057
Cell Rep. 2016 Mar 29;14(12):2819-32
pubmed: 26997270
Semin Immunol. 2000 Oct;12(5):475-85
pubmed: 11085180
J Gen Virol. 2015 Nov;96(11):3223-3235
pubmed: 26346306
Blood. 2006 Dec 1;108(12):3777-85
pubmed: 16896157
Cell. 2011 Oct 28;147(3):539-53
pubmed: 22036563
Methods Mol Biol. 2019;1576:33-42
pubmed: 27730537
J Immunol. 2010 Oct 15;185(8):4824-34
pubmed: 20861351
Transplantation. 1982 Aug;34(2):96-8
pubmed: 6753269
J Immunol. 2005 Oct 15;175(8):5213-21
pubmed: 16210626
Nat Biotechnol. 2008 Apr;26(4):453-61
pubmed: 18376399
Bone Marrow Transplant. 1990 Apr;5(4):209-26
pubmed: 2186835
Endocr Rev. 1996 Aug;17(4):369-84
pubmed: 8854050
J Exp Med. 2007 Jun 11;204(6):1267-72
pubmed: 17502664
Cell. 2010 Oct 29;143(3):355-66
pubmed: 21029859
Infect Immun. 2020 Mar 23;88(4):
pubmed: 31932328
Blood. 2011 Nov 24;118(22):5723-31
pubmed: 21908422
J Immunol. 2015 Dec 15;195(12):5678-87
pubmed: 26538393
J Immunol. 2013 Jun 15;190(12):6173-9
pubmed: 23686483
Blood. 2011 Aug 18;118(7):1962-70
pubmed: 21659540
J Exp Med. 1994 Nov 1;180(5):1955-60
pubmed: 7964471
J Immunol. 2015 Nov 1;195(9):4292-305
pubmed: 26416281
J Immunol. 2006 Jan 15;176(2):914-22
pubmed: 16393976
Stem Cell Reports. 2015 Mar 10;4(3):445-58
pubmed: 25733018
Blood. 2017 Aug 17;130(7):933-942
pubmed: 28607133
Gene Expr Patterns. 2006 Oct;6(8):794-9
pubmed: 16517216
Nat Cell Biol. 2014 Sep;16(9):902-8
pubmed: 25150981
JCI Insight. 2017 May 18;2(10):
pubmed: 28515359
J Immunol. 1994 May 15;152(10):5014-21
pubmed: 8176219
Front Endocrinol (Lausanne). 2018 May 01;9:214
pubmed: 29765355
Am J Hematol. 1997 Feb;54(2):131-8
pubmed: 9034287
J Exp Med. 2008 Jul 7;205(7):1701-14
pubmed: 18573906
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7172-7
pubmed: 8692964
Nat Immunol. 2002 Jul;3(7):635-42
pubmed: 12068292
J Immunol. 2009 Dec 1;183(11):7084-94
pubmed: 19890044
J Biol Chem. 2002 Sep 13;277(37):33676-82
pubmed: 12087100
J Immunol. 2000 Feb 15;164(4):1814-9
pubmed: 10657629
Cell Stem Cell. 2013 Aug 1;13(2):230-6
pubmed: 23910085
Eur J Immunol. 2005 Jul;35(7):2019-30
pubmed: 15971276
Blood. 1994 Oct 1;84(7):2221-8
pubmed: 7919339
Blood. 2004 Nov 1;104(9):2794-800
pubmed: 15226184
J Immunol. 1994 Feb 15;152(4):1609-17
pubmed: 7907102
Nature. 1998 Dec 17;396(6712):630-1
pubmed: 9872308
J Immunol. 2009 May 15;182(10):6247-60
pubmed: 19414778
J Exp Med. 2007 Oct 29;204(11):2521-8
pubmed: 17908938
Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9125-9
pubmed: 8415665
Cell Stem Cell. 2010 Mar 5;6(3):251-64
pubmed: 20207228
Nat Rev Cancer. 2010 Mar;10(3):213-21
pubmed: 20168320
Aging (Albany NY). 2009 Apr 22;1(4):389-401
pubmed: 20195490
Curr Opin Biotechnol. 2007 Oct;18(5):441-7
pubmed: 17702564
Blood. 2012 Aug 30;120(9):1820-30
pubmed: 22709689
J Bone Miner Res. 2012 Dec;27(12):2501-10
pubmed: 22836362
Nat Med. 2010 Aug;16(8):927-33
pubmed: 20628374
Biochem Pharmacol. 2020 Jan;171:113712
pubmed: 31726048
Eur J Immunol. 2011 Jul;41(7):1822-7
pubmed: 21706487
J Immunol. 2013 Jul 1;191(1):488-99
pubmed: 23709681
Lancet. 1961 Sep 30;2(7205):748-9
pubmed: 14474038
J Virol. 2005 Aug;79(15):9419-29
pubmed: 16014905
Cell Stem Cell. 2013 Aug 1;13(2):219-29
pubmed: 23684540
J Immunol. 2009 May 1;182(9):5846-54
pubmed: 19380833
Cell Death Dis. 2014 Oct 02;5:e1440
pubmed: 25275588
Clin Infect Dis. 2016 Apr 15;62(8):1029-1035
pubmed: 26908808
Blood. 2006 Mar 15;107(6):2453-60
pubmed: 16304055
EMBO Mol Med. 2017 Jun;9(6):835-851
pubmed: 28455312
Semin Immunol. 2007 Oct;19(5):331-40
pubmed: 18024073
Nat Cell Biol. 2010 Nov;12(11):1046-56
pubmed: 20972423
Blood. 2000 Dec 15;96(13):4350-6
pubmed: 11110712
Annu Rev Immunol. 2015;33:747-85
pubmed: 25706098
Nat Commun. 2014 Sep 18;5:4924
pubmed: 25233189
Science. 2005 Apr 8;308(5719):248-51
pubmed: 15705807
Immunity. 2002 Dec;17(6):749-56
pubmed: 12479821
Blood. 2002 Nov 1;100(9):3269-78
pubmed: 12384427
Cell Immunol. 2008 Mar-Apr;252(1-2):122-38
pubmed: 18294626
Nat Med. 2008 Feb;14(2):213-21
pubmed: 18193059
Blood. 1989 Apr;73(5):1340-50
pubmed: 2649174
Blood. 2003 Dec 1;102(12):3947-53
pubmed: 12920023
AIDS Res Hum Retroviruses. 1995 Jan;11(1):11-9
pubmed: 7734184
J Clin Invest. 2007 Oct;117(10):2778-90
pubmed: 17823656
Nat Rev Immunol. 2008 Jul;8(7):512-22
pubmed: 18469829
Blood. 2007 May 1;109(9):3803-11
pubmed: 17213286
J Clin Invest. 2010 Jan;120(1):343-56
pubmed: 19955659
Blood. 2009 Jul 30;114(5):972-82
pubmed: 19491395
J Exp Med. 1924 Aug 31;40(3):325-42
pubmed: 19868921
J Endocrinol. 1986 Sep;110(3):417-22
pubmed: 3760740
Br J Haematol. 1983 Mar;53(3):451-8
pubmed: 6218816
World J Orthop. 2012 Sep 18;3(9):142-50
pubmed: 23173110
Immunol Lett. 2013 Sep-Oct;155(1-2):31-5
pubmed: 24120996
Nat Methods. 2017 May;14(5):521-530
pubmed: 28369043
Eur J Immunol. 2016 Jun;46(6):1518-28
pubmed: 27125859
Blood. 2014 Jul 10;124(2):296-304
pubmed: 24876562
Immunotherapy. 2010 Jul;2(4):481-96
pubmed: 20636003
Biol Blood Marrow Transplant. 1997 Jun;3(2):65-75
pubmed: 9267666
J Immunol. 2015 Sep 15;195(6):2675-82
pubmed: 26254339
J Immunol. 2015 May 15;194(10):4784-95
pubmed: 25870244
AIDS Res Hum Retroviruses. 2006 Feb;22(2):163-70
pubmed: 16478398
Nat Rev Immunol. 2017 May;17(5):295-305
pubmed: 28317923
Blood. 2010 Mar 11;115(10):1897-905
pubmed: 19965655
Nat Methods. 2017 May;14(5):531-538
pubmed: 28394335
Immunity. 2001 Aug;15(2):261-73
pubmed: 11520461
Immunity. 2012 Aug 24;37(2):339-50
pubmed: 22921121
Eur J Immunol. 2007 Sep;37(9):2411-8
pubmed: 17694573
Semin Immunol. 2007 Oct;19(5):280-8
pubmed: 17997107
Int Immunol. 2002 Jul;14(7):813-22
pubmed: 12096041
Aging Cell. 2012 Feb;11(1):169-77
pubmed: 22103718
J Immunol. 2004 Sep 15;173(6):3816-24
pubmed: 15356129
Semin Immunopathol. 2008 Dec;30(4):439-56
pubmed: 18974988
J Leukoc Biol. 2008 Oct;84(4):915-23
pubmed: 18495786
Curr Stem Cell Rep. 2016 Jun;2(2):128-139
pubmed: 27529056
Clin Immunol. 2014 Jan;150(1):101-8
pubmed: 24333537
Front Immunol. 2019 Feb 05;10:25
pubmed: 30804925
J Immunol. 2012 Dec 15;189(12):5519-26
pubmed: 23152561
J Exp Med. 1995 Apr 1;181(4):1519-26
pubmed: 7699333
N Engl J Med. 1995 Jan 19;332(3):143-9
pubmed: 7800006
Blood. 2010 Mar 11;115(10):1906-12
pubmed: 20040757
Clin Immunol Immunopathol. 1994 Feb;70(2):152-8
pubmed: 7905366
Int J Immunopharmacol. 1995 Sep;17(9):703-18
pubmed: 8582782
Blood. 2013 Dec 19;122(26):4210-9
pubmed: 24215033
Cell Rep. 2014 Aug 21;8(4):1198-209
pubmed: 25131206
Clin Cancer Res. 2008 Feb 15;14(4):1138-49
pubmed: 18281548
Nat Rev Immunol. 2003 Nov;3(11):859-66
pubmed: 14668802
Blood. 2006 Aug 15;108(4):1216-22
pubmed: 16675711
J Exp Med. 2014 Nov 17;211(12):2341-9
pubmed: 25332287
Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3597-602
pubmed: 9520411
Stem Cell Reports. 2014 May 22;2(6):925-37
pubmed: 24936476
Dev Cell. 2013 Jul 29;26(2):204-19
pubmed: 23871589
JCI Insight. 2018 Mar 8;3(5):
pubmed: 29515037
Semin Immunopathol. 2008 Dec;30(4):479-87
pubmed: 19015856
J Exp Med. 2003 Jul 21;198(2):325-32
pubmed: 12860931
Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):961-6
pubmed: 18195351
Front Immunol. 2019 Mar 29;10:629
pubmed: 30984193
Toxicol Pathol. 1999 Jan-Feb;27(1):64-71
pubmed: 10367676
Blood. 2001 Dec 15;98(13):3505-12
pubmed: 11739150
Nature. 1980 Apr 10;284(5756):555-6
pubmed: 6245367
Front Immunol. 2017 Dec 05;8:1717
pubmed: 29259606
Blood. 2002 Jul 15;100(2):682-91
pubmed: 12091365
Biol Blood Marrow Transplant. 2019 Oct;25(10):1911-1919
pubmed: 31195136
Proc Natl Acad Sci U S A. 2006 Sep 5;103(36):13457-62
pubmed: 16938836
Bone Marrow Transplant. 1995 Sep;16(3):413-25
pubmed: 8535315
Parasite Immunol. 2015 Jul;37(7):349-61
pubmed: 25886201
Nature. 2014 Jan 2;505(7481):97-102
pubmed: 24256728
Br J Haematol. 2001 Dec;115(3):630-41
pubmed: 11736948
Immun Ageing. 2020 Jan 20;17:2
pubmed: 31988649
Blood. 1999 Jan 15;93(2):467-80
pubmed: 9885208
Blood. 2011 Aug 18;118(7):1715-6
pubmed: 21852443
Clin Exp Immunol. 1978 May;32(2):346-51
pubmed: 307469
Immunol Res. 2001;23(2-3):281-8
pubmed: 11444393
J Immunol. 2001 Aug 15;167(4):1954-61
pubmed: 11489975
Science. 2012 Apr 6;336(6077):91-5
pubmed: 22383805
N Engl J Med. 1997 Mar 27;336(13):897-904
pubmed: 9070469
Blood. 2011 Sep 22;118(12):3410-8
pubmed: 21791423
J Biol Chem. 2000 Oct 6;275(40):31335-9
pubmed: 10875937
J Leukoc Biol. 2017 Feb;101(2):543-554
pubmed: 27630218
Sci Immunol. 2018 Jan 12;3(19):
pubmed: 29330161
PLoS Pathog. 2006 Jun;2(6):e62
pubmed: 16846255
Blood. 2015 Apr 23;125(17):2720-3
pubmed: 25691159
J Immunol. 2007 Mar 15;178(6):3551-7
pubmed: 17339451
Blood. 2012 Dec 6;120(24):4882-91
pubmed: 23012326
Front Endocrinol (Lausanne). 2018 Jul 12;9:381
pubmed: 30050502
Immunity. 1995 Jan;2(1):25-36
pubmed: 7600300
Cell Stem Cell. 2009 Mar 6;4(3):263-74
pubmed: 19265665
J Immunol. 2007 Jun 1;178(11):7473-84
pubmed: 17513799
J Exp Med. 2006 Oct 2;203(10):2263-9
pubmed: 16966427
Annu Rev Immunol. 2000;18:309-45
pubmed: 10837061
Nat Med. 2006 Sep;12(9):1039-47
pubmed: 16936725
J Immunol. 2005 Jun 1;174(11):6571-6
pubmed: 15905493
Mol Cancer Res. 2018 Nov;16(11):1652-1664
pubmed: 30006356
Immunol Rev. 2008 Oct;225:68-84
pubmed: 18837776
Biol Blood Marrow Transplant. 1995 Nov;1(1):18-23
pubmed: 9118285
J Immunol. 2005 Aug 15;175(4):2741-53
pubmed: 16081852
Immunol Rev. 1997 Jun;157:73-8
pubmed: 9255623
Clin Infect Dis. 2011 Nov;53(9):944-51
pubmed: 21960716
AIDS. 2014 Jan 14;28(2):209-14
pubmed: 24072195
Blood. 2007 Dec 15;110(13):4543-51
pubmed: 17671230
Blood. 2008 Jun 15;111(12):5734-44
pubmed: 18334670
Clin Infect Dis. 2009 Nov 1;49(9):1454-6
pubmed: 19824851
J Immunol. 2010 Jun 1;184(11):6014-24
pubmed: 20483779
Immunity. 2002 Jun;16(6):803-14
pubmed: 12121662
Lancet. 1987 Jul 25;2(8552):175-8
pubmed: 2885638
Mol Ther. 2015 Jul;23(7):1262-1277
pubmed: 25903472
Transplantation. 2000 May 27;69(10):2190-3
pubmed: 10852622
J Exp Med. 2008 Mar 17;205(3):523-31
pubmed: 18299401
Nat Biotechnol. 2019 Mar;37(3):293-302
pubmed: 30742125
J Clin Invest. 2016 Mar 1;126(3):1126-36
pubmed: 26901814
J Exp Med. 2018 Apr 2;215(4):1069-1077
pubmed: 29472496
Immunity. 2008 Sep 19;29(3):438-50
pubmed: 18799150
Blood. 2008 Oct 15;112(8):3255-63
pubmed: 18694999
J Clin Invest. 1999 Oct;104(8):1051-9
pubmed: 10525043