Murine Models of Familial Cytokine Storm Syndromes.
CTL
Cytotoxicity
Disease-causing mutation
HLH
Hyper inflammation
Immune dysregulation
Inflammatory cytokine
Mouse
Murine model
NK cell
Perforin
Virus infection
Journal
Advances in experimental medicine and biology
ISSN: 0065-2598
Titre abrégé: Adv Exp Med Biol
Pays: United States
ID NLM: 0121103
Informations de publication
Date de publication:
2024
2024
Historique:
medline:
9
8
2024
pubmed:
9
8
2024
entrez:
8
8
2024
Statut:
ppublish
Résumé
Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disease caused by mutations in effectors and regulators of cytotoxicity in cytotoxic T cells (CTL) and natural killer (NK) cells. The complexity of the immune system means that in vivo models are needed to efficiently study diseases like HLH. Mice with defects in the genes known to cause primary HLH (pHLH) are available. However, these mice only develop the characteristic features of HLH after the induction of an immune response (typically through infection with lymphocytic choriomeningitis virus). Nevertheless, murine models have been invaluable for understanding the mechanisms that lead to HLH. For example, the cytotoxic machinery (e.g., the transport of cytotoxic vesicles and the release of granzymes and perforin after membrane fusion) was first characterized in the mouse. Experiments in murine models of pHLH have emphasized the importance of cytotoxic cells, antigen-presenting cells (APC), and cytokines in hyperinflammatory positive feedback loops (e.g., cytokine storms). This knowledge has facilitated the development of treatments for human HLH, some of which are now being tested in the clinic.
Identifiants
pubmed: 39117835
doi: 10.1007/978-3-031-59815-9_33
doi:
Substances chimiques
Cytokines
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
481-496Informations de copyright
© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.
Références
Blake JA, et al. Mouse Genome Database (MGD)-2017: Community knowledge resource for the laboratory mouse. Nucleic Acids Res. 2017;45:D723–9.
pubmed: 27899570
doi: 10.1093/nar/gkw1040
Abolins S, et al. The comparative immunology of wild and laboratory mice, Mus musculus domesticus. Nat Commun. 2017;8:14811.
pubmed: 28466840
pmcid: 5418598
doi: 10.1038/ncomms14811
Castrop H. Genetically modified mice-successes and failures of a widely used technology. Pflugers Arch Eur J Physiol. 2010;459:557–67.
doi: 10.1007/s00424-009-0770-z
Justice MJ, Siracusa LD, Stewart AF. Technical approaches for mouse models of human disease. Dis Model Mech. 2011;4:305–10.
pubmed: 21558063
pmcid: 3097452
doi: 10.1242/dmm.000901
Gierut JJ, Jacks TE, Haigis KM. Strategies to achieve conditional gene mutation in mice. Cold Spring Harb Protoc. 2014;2014:339–49.
pubmed: 24692485
pmcid: 4142476
doi: 10.1101/pdb.top069807
Perlman RL. Mouse models of human disease: an evolutionary perspective. Evol Med Public Health. 2016;eow014 https://doi.org/10.1093/emph/eow014 .
Henter J-I, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48:124–31.
pubmed: 16937360
doi: 10.1002/pbc.21039
Doran AG, et al. Deep genome sequencing and variation analysis of 13 inbred mouse strains defines candidate phenotypic alleles, private variation and homozygous truncating mutations. Genome Biol. 2016;17:167.
pubmed: 27480531
pmcid: 4968449
doi: 10.1186/s13059-016-1024-y
Sellers RS, Clifford CB, Treuting PM, Brayton C. Immunological variation between inbred laboratory mouse strains. Vet Pathol. 2012;49:32–43.
pubmed: 22135019
doi: 10.1177/0300985811429314
Brisse E, Wouters CH, Matthys P. Hemophagocytic lymphohistiocytosis (HLH): a heterogeneous spectrum of cytokine-driven immune disorders. Cytokine Growth Factor Rev. 2015;26:263–80.
pubmed: 25466631
doi: 10.1016/j.cytogfr.2014.10.001
Kägi D, et al. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature. 1994;369:31–7.
pubmed: 8164737
doi: 10.1038/369031a0
Walsh CM, et al. Immune function in mice lacking the perforin gene. Proc Natl Acad Sci USA. 1994;91:10854–8.
pubmed: 7526382
pmcid: 45124
doi: 10.1073/pnas.91.23.10854
Jordan MB, Hildeman D, Kappler J, Marrack P. An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8 + T cells and interferon gamma are essential for the disorder. Blood. 2004;104:735–43.
pubmed: 15069016
doi: 10.1182/blood-2003-10-3413
Badovinac VP, Hamilton SE, Harty JT. Viral infection results in massive CD8+ T cell expansion and mortality in vaccinated perforin-deficient mice. Immunity. 2003;18:463–74.
pubmed: 12705850
doi: 10.1016/S1074-7613(03)00079-7
Lowin B, Beermann F, Schmidt A, Tschopp J. A null mutation in the perforin gene impairs cytolytic T lymphocyte- and natural killer cell-mediated cytotoxicity. Proc Natl Acad Sci USA. 1994;91:11571–5.
pubmed: 7972104
pmcid: 45273
doi: 10.1073/pnas.91.24.11571
Lowin B, Hahne M, Mattmann C, Tschopp J. Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature. 1994;370:650–2.
pubmed: 7520535
doi: 10.1038/370650a0
Spielman J, Lee RK, Podack ER. Perforin/Fas-ligand double deficiency is associated with macrophage expansion and severe pancreatitis. J Immunol. 1998;161:7063–70.
pubmed: 9862744
doi: 10.4049/jimmunol.161.12.7063
Kägi D, et al. Reduced incidence and delayed onset of diabetes in perforin-deficient nonobese diabetic mice. J Exp Med. 1997;186:989–97.
pubmed: 9314549
pmcid: 2199062
doi: 10.1084/jem.186.7.989
Müllbacher A, Hla RT, Museteanu C, Simon MM. Perforin is essential for control of ectromelia virus but not related poxviruses in mice. J Virol. 1999;73:1665–7.
pubmed: 9882377
pmcid: 103996
doi: 10.1128/JVI.73.2.1665-1667.1999
Chang E, Galle L, Maggs D, Estes DM, Mitchell WJ. Pathogenesis of Herpes simplex virus type 1-induced corneal inflammation in perforin-deficient mice. J Virol. 2000;74:11832–40.
pubmed: 11090183
pmcid: 112466
doi: 10.1128/JVI.74.24.11832-11840.2000
van Dommelen SLH, et al. Perforin and granzymes have distinct roles in defensive immunity and immunopathology. Immunity. 2006;25:835–48.
pubmed: 17088087
doi: 10.1016/j.immuni.2006.09.010
Schmidt NW, Khanolkar A, Hancox L, Heusel JW, Harty JT. Perforin plays an unexpected role in regulating T-cell contraction during prolonged listeria monocytogenes infection. Eur J Immunol. 2012;42:629–40.
pubmed: 22161269
pmcid: 3418886
doi: 10.1002/eji.201141902
Gupta M, et al. CD8-mediated protection against Ebola virus infection is perforin dependent. J Immunol. 2005;174:4198–202.
pubmed: 15778381
doi: 10.4049/jimmunol.174.7.4198
Wirtz T, et al. Mouse model for acute Epstein-Barr virus infection. Proc Natl Acad Sci USA. 2016;113:201616574.
doi: 10.1073/pnas.1616574113
Badovinac VP. Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-gamma. Science. 2000;1979(290):1354–7.
doi: 10.1126/science.290.5495.1354
Pham NLL, Badovinac VP, Harty JT. Epitope specificity of memory CD8 + T cells dictates vaccination-induced mortality in LCMV-infected perforin-deficient mice. Eur J Immunol. 2012;42:1488–99.
pubmed: 22678903
pmcid: 3650624
doi: 10.1002/eji.201142263
Yang J, Huck SP, McHugh RS, Hermans IF, Ronchese F. Perforin-dependent elimination of dendritic cells regulates the expansion of antigen-specific CD8+ T cells in vivo. Proc Natl Acad Sci USA. 2006;103:147–52.
pubmed: 16373503
doi: 10.1073/pnas.0509054103
Terrell CE, Jordan MB. Perforin deficiency impairs a critical immunoregulatory loop involving murine CD8(+) T cells and dendritic cells. Blood. 2013;121:5184–91.
pubmed: 23660960
pmcid: 3695362
doi: 10.1182/blood-2013-04-495309
Terrell CE, Jordan MB. Mixed hematopoietic or T-cell chimerism above a minimal threshold restores perforin-dependent immune regulation in perforin-deficient mice. Blood. 2013;122:2618–21.
pubmed: 23974195
pmcid: 3795460
doi: 10.1182/blood-2013-06-508143
Waggoner SN, Taniguchi RT, Mathew PA, Kumar V, Welsh RM. Absence of mouse 2B4 promotes NK cell-mediated killing of activated CD8+ T cells, leading to prolonged viral persistence and altered pathogenesis. J Clin Invest. 2010;120:1925–38.
pubmed: 20440077
pmcid: 2877945
doi: 10.1172/JCI41264
Lang PA, et al. Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8+ T-cell immunity. Proc Natl Acad Sci. 2012;109:1210–5.
pubmed: 22167808
doi: 10.1073/pnas.1118834109
Ge MQ, et al. NK cells regulate CD8+ T cell priming and dendritic cell migration during influenza A infection by IFN-γ and perforin-dependent mechanisms. J Immunol. 2012;189:2099–109.
pubmed: 22869906
doi: 10.4049/jimmunol.1103474
Zangi L, et al. Deletion of cognate CD8 T cells by immature dendritic cells: a novel role for perforin, granzyme A, TREM-1, and TLR7. Blood. 2012;120:1647–57.
pubmed: 22776817
doi: 10.1182/blood-2012-02-410803
Sepulveda FE, et al. A novel immunoregulatory role for NK-cell cytotoxicity in protection from HLH-like immunopathology in mice. Blood. 2015;125:1427–34.
pubmed: 25525117
doi: 10.1182/blood-2014-09-602946
Waggoner SN, Kumar V. Evolving role of 2B4/CD244 in T and NK cell responses during virus infection. Front Immunol. 2012;3:377.
pubmed: 23248626
pmcid: 3518765
doi: 10.3389/fimmu.2012.00377
Madera S, et al. Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide. J Exp Med. 2016;jem.20150712 https://doi.org/10.1084/jem.20150712 .
Crouse J, et al. Type I interferons protect T cells against NK cell attack mediated by the activating receptor NCR1. Immunity. 2014;40:961–73.
pubmed: 24909889
doi: 10.1016/j.immuni.2014.05.003
Xu HC, et al. Type I interferon protects antiviral CD8+ T cells from NK cell cytotoxicity. Immunity. 2014;40:949–60.
pubmed: 24909887
doi: 10.1016/j.immuni.2014.05.004
Jenkins MR, et al. Failed CTL/NK cell killing and cytokine hypersecretion are directly linked through prolonged synapse time. J Exp Med. 2015;212:307–17.
pubmed: 25732304
pmcid: 4354371
doi: 10.1084/jem.20140964
Binder D, et al. Aplastic anemia rescued by exhaustion of cytokine-secreting CD8+ T cells in persistent infection with lymphocytic choriomeningitis virus. J Exp Med. 1998;187:1903–20.
pubmed: 9607930
pmcid: 2212311
doi: 10.1084/jem.187.11.1903
Pachlopnik-Schmid J, et al. Neutralization of IFNγ defeats haemophagocytosis in LCMV-infected perforin- and Rab27a-deficient mice. EMBO Mol Med. 2009;1:112–24.
pubmed: 20049711
doi: 10.1002/emmm.200900009
Rood JE, et al. ST2 contributes to T-cell hyperactivation and fatal hemophagocytic lymphohistiocytosis in mice. Blood. 2016;127:426–35.
pubmed: 26518437
pmcid: 4731846
doi: 10.1182/blood-2015-07-659813
Humblet-Baron S, et al. IL-2 consumption by highly activated CD8 T cells induces regulatory T-cell dysfunction in patients with hemophagocytic lymphohistiocytosis. J Allergy Clin Immunol. 2016;138:200–209.e8.
pubmed: 26947179
doi: 10.1016/j.jaci.2015.12.1314
Das R, et al. Janus kinase inhibition lessens inflammation and ameliorates disease in murine models of hemophagocytic lymphohistiocytosis. Blood. 2016;127:1666–75.
pubmed: 26825707
pmcid: 4817310
doi: 10.1182/blood-2015-12-684399
Maschalidi S, Sepulveda FE, Garrigue A, Fischer A, de Saint Basile G. Therapeutic effect of JAK1/2 blockade on the manifestations of hemophagocytic lymphohistiocytosis in mice. Blood. 2016;128:60–71.
pubmed: 27222478
doi: 10.1182/blood-2016-02-700013
Keenan C, Nichols KE, Albeituni S. Use of the JAK inhibitor Ruxolitinib in the treatment of hemophagocytic lymphohistiocytosis. Front Immunol. 2021;12
Albeituni S, et al. Mechanisms of action of ruxolitinib in murine models of hemophagocytic lymphohistiocytosis. Blood. 2019;134:147–59.
pubmed: 31015190
pmcid: 6624972
doi: 10.1182/blood.2019000761
Chaturvedi V, Lakes N, Tran M, Castillo N, Jordan MB. JAK inhibition for murine HLH requires complete blockade of IFN-γ signaling and is limited by toxicity of JAK2 inhibition. Blood. 2021;138:1034–9.
pubmed: 34232994
doi: 10.1182/blood.2020007930
Crozat K, et al. Analysis of the MCMV resistome by ENU mutagenesis. Mamm Genome. 2006;17:398–406.
pubmed: 16688530
doi: 10.1007/s00335-005-0164-2
Crozat K, et al. Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis. J Exp Med. 2007;204:853–63.
pubmed: 17420270
pmcid: 2118559
doi: 10.1084/jem.20062447
Krebs P, Crozat K, Popkin D, Oldstone MB, Beutler B. Disruption of MyD88 signaling suppresses hemophagocytic lymphohistiocytosis in mice. Blood. 2011;117:6582–8.
pubmed: 21551232
pmcid: 3123024
doi: 10.1182/blood-2011-01-329607
Monfregola J, Johnson JL, Meijler MM, Napolitano G, Catz SD. MUNC13-4 protein regulates the oxidative response and is essential for phagosomal maturation and bacterial killing in neutrophils. J Biol Chem. 2012;287:44603–18.
pubmed: 23115246
pmcid: 3531776
doi: 10.1074/jbc.M112.414029
He J, et al. Munc13-4 interacts with syntaxin 7 and regulates late endosomal maturation, endosomal signaling, and TLR9-initiated cellular responses. Mol Biol Cell. 2016;27:572–87.
pubmed: 26680738
pmcid: 4751605
doi: 10.1091/mbc.e15-05-0283
Johnson JL, et al. Munc13-4 is a Rab11-binding protein that regulates Rab11-positive vesicle trafficking and docking at the plasma membrane. J Biol Chem. 2016;291:3423–38.
pubmed: 26637356
doi: 10.1074/jbc.M115.705871
Chicka MC, et al. Role of Munc13-4 as a Ca2+−dependent tether during platelet secretion. Biochem J. 2016;473:627–39.
pubmed: 26637270
doi: 10.1042/BJ20151150
D’Orlando O, et al. Syntaxin 11 is required for NK and CD8+ T-cell cytotoxicity and neutrophil degranulation. Eur J Immunol. 2013;43:194–208.
pubmed: 23042080
doi: 10.1002/eji.201142343
Sepulveda FE, et al. Distinct severity of HLH in both human and murine mutants with complete loss of cytotoxic effector PRF1, RAB27A, and STX11. Blood. 2013;121:595–603.
pubmed: 23160464
doi: 10.1182/blood-2012-07-440339
Kogl T, et al. Hemophagocytic lymphohistiocytosis in syntaxin-11-deficient mice: T-cell exhaustion limits fatal disease. Blood. 2013;121:604–13.
pubmed: 23190531
doi: 10.1182/blood-2012-07-441139
Prekeris R, Klumperman J, Scheller RH. Syntaxin 11 is an atypical SNARE abundant in the immune system. Eur J Cell Biol. 2000;79:771–80.
pubmed: 11139139
doi: 10.1078/0171-9335-00109
Ye S, et al. Syntaxin-11, but not syntaxin-2 or syntaxin-4, is required for platelet secretion. Blood. 2012;120:2484–92.
pubmed: 22767500
pmcid: 3448260
doi: 10.1182/blood-2012-05-430603
Zhang S, et al. Syntaxin-11 is expressed in primary human monocytes/macrophages and acts as a negative regulator of macrophage engulfment of apoptotic cells and IgG-opsonized target cells. Br J Haematol. 2008;142:469–79.
pubmed: 18547321
doi: 10.1111/j.1365-2141.2008.07191.x
Kim K, et al. Munc18b is an essential gene in mice whose expression is limiting for secretion by airway epithelial and mast cells. Biochem J. 2012;446:383–94.
pubmed: 22694344
doi: 10.1042/BJ20120057
Spessott WA, et al. Hemophagocytic lymphohistiocytosis caused by dominant-negative mutations in STXBP2 that inhibit SNARE-mediated membrane fusion. Blood. 2015;125:1566–77.
pubmed: 25564401
pmcid: 4351505
doi: 10.1182/blood-2014-11-610816
Silvers WK. The coat colors of mice. New York: Springer; 1979. https://doi.org/10.1007/978-1-4612-6164-3 .
doi: 10.1007/978-1-4612-6164-3
Wilson SM, et al. A mutation in Rab27a causes the vesicle transport defects observed in ashen mice. Proc Natl Acad Sci. 2000;97:7933–8.
pubmed: 10859366
pmcid: 16648
doi: 10.1073/pnas.140212797
Stinchcombe JC, et al. Rab27a is required for regulating secretion in cytotoxic T lymphocytes. J Cell Biol. 2001;152:825–33.
pubmed: 11266472
pmcid: 2195783
doi: 10.1083/jcb.152.4.825
Novak EK, et al. The regulation of platelet-dense granules by Rab27a in the ashen mouse, a model of Hermansky-Pudlak and Griscelli syndromes, is granule-specific and dependent on genetic background. Blood. 2002;100:128–35.
pubmed: 12070017
doi: 10.1182/blood.V100.1.128
Pachlopnik Schmid J, et al. A Griscelli syndrome type 2 murine model of hemophagocytic lymphohistiocytosis (HLH). Eur J Immunol. 2008;38:3219–25.
pubmed: 18991284
doi: 10.1002/eji.200838488
Johnson JL, Hong H, Monfregola J, Catz SD. Increased survival and reduced neutrophil infiltration of the liver in rab27a- but not munc13-4-deficient mice in lipopolysaccharide-induced systemic inflammation. Infect Immun. 2011;79:3607–18.
pubmed: 21746860
pmcid: 3165471
doi: 10.1128/IAI.05043-11
Bennett JM, Blume RS, Wolff SM. Characterization and significance of abnormal leukocyte granules in the beige mouse: a possible homologue for Chediak-Higashi Aleutian trait. Transl Res. 1969;73:235–43.
Oliver C, Essner E. Formation of anomalous lysosomes in monocytes, neutrophils, and eosinophils from bone marrow of mice with Chédiak-Higashi syndrome. Lab Investig. 1975;32:17–27.
pubmed: 1113502
Orn A, et al. Pigment mutations in the mouse which also affect lysosomal functions lead to suppressed natural killer cell activity. Scand J Immunol. 1982;15:305–10.
pubmed: 7089489
doi: 10.1111/j.1365-3083.1982.tb00653.x
Roder J, Duwe A. The beige mutation in the mouse selectively impairs natural killer cell function. Nature. 1979;278:451–3.
pubmed: 313007
doi: 10.1038/278451a0
Kärre K, Klein GO, Kiessling R, Klein G, Roder JC. Low natural in vivo resistance to syngeneic leukaemias in natural killer-deficient mice. Nature. 1980;284:624–6.
pubmed: 7366734
doi: 10.1038/284624a0
Barbosa, M. D. F. S. et al. Identification of the homologous beige and Chediak–Higashi syndrome genes. Nature 382, 262–265 (1996).
McGarry MP, Reddington M, Novak EK, Swank RT. Survival and lung pathology of mouse models of Hermansky-Pudlak syndrome and Chediak-Higashi syndrome. Proc Soc Exp Biol Med. 1999;220:162–8.
pubmed: 10193444
Jessen B, et al. Subtle differences in CTL cytotoxicity determine susceptibility to hemophagocytic lymphohistiocytosis in mice and humans with Chediak-Higashi syndrome. Blood. 2011;118:4620–9.
pubmed: 21878672
doi: 10.1182/blood-2011-05-356113
Chatterjee P, Tiwari RK, Rath S, Bal V, George A. Modulation of antigen presentation and B cell receptor signaling in B cells of beige mice. J Immunol. 2012;188:2695–702.
pubmed: 22327079
doi: 10.4049/jimmunol.1101527
Westphal A, et al. Lysosomal trafficking regulator Lyst links membrane trafficking to toll-like receptor–mediated inflammatory responses. J Exp Med. 2016;214:jem.20141461.
Balkema GW, Mangini NJ, Pinto LH. Discrete visual defects in pearl mutant mice. Science. 1983;219:1085–7.
pubmed: 6600521
doi: 10.1126/science.6600521
Novak EK, Hui SW, Swank RT. Platelet storage pool deficiency in mouse pigment mutations associated with seven distinct genetic loci. Blood. 1984;63:536–44.
pubmed: 6696991
doi: 10.1182/blood.V63.3.536.536
Zhen L, et al. Abnormal expression and subcellular distribution of subunit proteins of the AP-3 adaptor complex lead to platelet storage pool deficiency in the pearl mouse. Blood. 1999;94:146–55.
pubmed: 10381507
doi: 10.1182/blood.V94.1.146.413k39_146_155
Feng L, et al. The β3A subunit gene (Ap3b1) of the AP-3 adaptor complex is altered in the mouse hypopigmentation mutant pearl, a model for Hermansky-Pudlak syndrome and night blindness. Hum Mol Genet. 1999;8:323–30.
pubmed: 9931340
doi: 10.1093/hmg/8.2.323
Feng L, Rigatti BW, Novak EK, Gorin MB, Swank RT. Genomic structure of the mouse Ap3b1 gene in normal and pearl mice. Genomics. 2000;69:370–9.
pubmed: 11056055
doi: 10.1006/geno.2000.6350
Yang W, Li C, Ward DM, Kaplan J, Mansour SL. Defective organellar membrane protein trafficking in Ap3b1-deficient cells. J Cell Sci. 2000;113(Pt 2):4077–86.
pubmed: 11058094
doi: 10.1242/jcs.113.22.4077
Swank RT, et al. Abnormal vesicular trafficking in mouse models of Hermansky-Pudlak syndrome. Pigment Cell Res. 2000;13(Suppl 8):59–67.
pubmed: 11041359
doi: 10.1034/j.1600-0749.13.s8.12.x
Cernadas M, et al. Lysosomal localization of murine CD1d mediated by AP-3 is necessary for NK T cell development. J Immunol. 2003;171:4149–55.
pubmed: 14530337
doi: 10.4049/jimmunol.171.8.4149
Young LR, Borchers MT, Allen HL, Gibbons RS, McCormack FX. Lung-restricted macrophage activation in the pearl mouse model of Hermansky-Pudlak syndrome. J Immunol. 2006;176:4361–8.
pubmed: 16547274
doi: 10.4049/jimmunol.176.7.4361
Meng R, et al. Defective release of α granule and lysosome contents from platelets in mouse Hermansky-Pudlak syndrome models. Blood. 2015;125:1623–32.
pubmed: 25477496
pmcid: 4351507
doi: 10.1182/blood-2014-07-586727
Jessen B, et al. The risk of hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type 2. Blood. 2013;121:2943–51.
pubmed: 23403622
pmcid: 3624940
doi: 10.1182/blood-2012-10-463166
Czar MJ, et al. Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP. Proc Natl Acad Sci. 2001;98:7449–54.
pubmed: 11404475
pmcid: 34689
doi: 10.1073/pnas.131193098
Wu C, et al. SAP controls T cell responses to virus and terminal differentiation of TH2 cells. Nat Immunol. 2001;2:410–4.
pubmed: 11323694
doi: 10.1038/87713
Crotty S, Kersh EN, Cannons J, Schwartzberg PL, Ahmed R. SAP is required for generating long-term humoral immunity. Nature. 2003;421:282–7.
pubmed: 12529646
doi: 10.1038/nature01318
Chan B, et al. SAP couples Fyn to SLAM immune receptors. Nat Cell Biol. 2003;5:155–60.
pubmed: 12545174
doi: 10.1038/ncb920
Latour S, et al. Binding of SAP SH2 domain to FynT SH3 domain reveals a novel mechanism of receptor signalling in immune regulation. Nat Cell Biol. 2003;5:149–54.
pubmed: 12545173
doi: 10.1038/ncb919
Qi H, Cannons JL, Klauschen F, Schwartzberg PL, Germain RN. SAP-controlled T-B cell interactions underlie germinal centre formation. Nature. 2008;455:764–9.
pubmed: 18843362
pmcid: 2652134
doi: 10.1038/nature07345
Veillette A, et al. SAP expression in T cells, not in B cells, is required for humoral immunity. Proc Natl Acad Sci USA. 2008;105:1273–8.
pubmed: 18212118
pmcid: 2234128
doi: 10.1073/pnas.0710698105
Nichols KE, et al. Regulation of NKT cell development by SAP, the protein defective in XLP. Nat Med. 2005;11:340–5.
pubmed: 15711562
pmcid: 10655637
doi: 10.1038/nm1189
Pasquier B, et al. Defective NKT cell development in mice and humans lacking the adapter SAP, the X-linked lymphoproliferative syndrome gene product. J Exp Med. 2005;201:695–701.
pubmed: 15738056
pmcid: 2212840
doi: 10.1084/jem.20042432
Das R, et al. The adaptor molecule SAP plays essential roles during invariant NKT cell cytotoxicity and lytic synapse formation. Blood. 2013;121:3386–95.
pubmed: 23430111
pmcid: 3637014
doi: 10.1182/blood-2012-11-468868
Yin L, et al. Mice deficient in the X-linked lymphoproliferative disease gene sap exhibit increased susceptibility to murine gammaherpesvirus-68 and hypo-gammaglobulinemia. J Med Virol. 2003;71:446–55.
pubmed: 12966553
doi: 10.1002/jmv.10504
Crotty S, McCausland MM, Aubert RD, Wherry EJ, Ahmed R. Hypogammaglobulinemia and exacerbated CD8 T-cell-mediated immunopathology in SAP-deficient mice with chronic LCMV infection mimics human XLP disease. Blood. 2006;108:3085–93.
pubmed: 16788096
doi: 10.1182/blood-2006-04-018929
Dong Z, et al. The adaptor SAP controls NK cell activation by regulating the enzymes Vav-1 and SHIP-1 and by enhancing conjugates with target cells. Immunity. 2012;36:974–85.
pubmed: 22683124
doi: 10.1016/j.immuni.2012.03.023
Rivat C, et al. SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease. Blood. 2013;121:1073–6.
pubmed: 23223356
pmcid: 3779401
doi: 10.1182/blood-2012-07-445858
Ruffo E, et al. Inhibition of diacylglycerol kinase α restores restimulation-induced cell death and reduces immunopathology in XLP-1. Sci Transl Med. 2016;8:321ra7.
pubmed: 26764158
pmcid: 4918505
doi: 10.1126/scitranslmed.aad1565
Harlin H, et al. Characterization of XIAP-deficient mice. Mol Cell Biol. 2001;21:3604–8.
pubmed: 11313486
pmcid: 100282
doi: 10.1128/MCB.21.10.3604-3608.2001
Olayioye MA, et al. XIAP-deficiency leads to delayed lobuloalveolar development in the mammary gland. Cell Death Differ. 2005;12:87–90.
pubmed: 15540113
doi: 10.1038/sj.cdd.4401524
Bauler LD, Duckett CS, O’Riordan MXD. XIAP regulates cytosol-specific innate immunity to listeria infection. PLoS Pathog. 2008;4
Rumble JM, et al. Apoptotic sensitivity of murine IAP-deficient cells. Biochem J. 2008;415:21–5.
pubmed: 18684108
doi: 10.1042/BJ20081188
Schile AJ, García-Fernández M, Steller H. Regulation of apoptosis by XIAP ubiquitin-ligase activity. Genes Dev. 2008;22:2256–66.
pubmed: 18708583
pmcid: 2518817
doi: 10.1101/gad.1663108
Jost PJ, et al. XIAP discriminates between type I and type II FAS-induced apoptosis. Nature. 2009;460:1035–9.
pubmed: 19626005
pmcid: 2956120
doi: 10.1038/nature08229
Prakash H, Albrecht M, Becker D, Kuhlmann T, Rudel T. Deficiency of XIAP leads to sensitization for Chlamydophila pneumoniae pulmonary infection and dysregulation of innate immune response in mice. J Biol Chem. 2010;285:20291–302.
pubmed: 20427267
pmcid: 2888442
doi: 10.1074/jbc.M109.096297
Fuchs Y, et al. Sept4/ARTS regulates stem cell apoptosis and skin regeneration. Science. 2013;341:286–9.
pubmed: 23788729
pmcid: 4358763
doi: 10.1126/science.1233029
Unsain N, Higgins JM, Parker KN, Johnstone AD, Barker PA. XIAP regulates caspase activity in degenerating axons. Cell Rep. 2013;4:751–63.
pubmed: 23954782
doi: 10.1016/j.celrep.2013.07.015
Yabal M, et al. XIAP restricts TNF- and RIP3-dependent cell death and Inflammasome activation. Cell Rep. 2014;7:1796–808.
pubmed: 24882010
doi: 10.1016/j.celrep.2014.05.008
Andree M, et al. BID-dependent release of mitochondrial SMAC dampens XIAP-mediated immunity against Shigella. EMBO J. 2014;33:2171–87.
pubmed: 25056906
pmcid: 4282505
doi: 10.15252/embj.201387244
Hsieh W-C, et al. Inability to resolve specific infection generates innate immunodeficiency syndrome in Xiap−/− mice. Blood. 2014;124:2847–57.
pubmed: 25190756
doi: 10.1182/blood-2014-03-564609
Gentle IE, et al. Inhibitor of apoptosis proteins (IAPs) are required for effective T cell expansion/survival during anti-viral immunity in mice. Blood. 2013;123:659–69.
pubmed: 24335231
doi: 10.1182/blood-2013-01-479543
Ebert G, et al. Cellular inhibitor of apoptosis proteins prevent clearance of hepatitis B virus. Proc Natl Acad Sci USA. 2015;112:5797–802.
pubmed: 25902529
pmcid: 4426461
doi: 10.1073/pnas.1502390112
Gibon J, et al. The X-linked inhibitor of apoptosis regulates long-term depression and learning rate. FASEB J. 2016;30:1–8.
doi: 10.1096/fj.201600384R
González-Cabrero J, et al. CD48-deficient mice have a pronounced defect in CD4(+) T cell activation. Proc Natl Acad Sci USA. 1999;96:1019–23.
pubmed: 9927686
pmcid: 15343
doi: 10.1073/pnas.96.3.1019
Volkmer B, et al. Recurrent inflammatory disease caused by a heterozygous mutation in CD48. J Allergy Clin Immunol. 2019;144:1441–1445.e17.
pubmed: 31419545
doi: 10.1016/j.jaci.2019.07.038
Chen M, Felix K, Wang J. Critical role for perforin and Fas-dependent killing of dendritic cells in the control of inflammation. Blood. 2012;119:127–36.
pubmed: 22042696
pmcid: 3251225
doi: 10.1182/blood-2011-06-363994
Tsoukas P, et al. Interleukin-18 and cytotoxic impairment are independent and synergistic causes of murine virus-induced hyperinflammation. Blood. 2020;136:2162–74.
pubmed: 32589707
pmcid: 7645987
doi: 10.1182/blood.2019003846
Nansen A, et al. Compromised virus control and augmented perforin-mediated immunopathology in IFN-gamma-deficient mice infected with lymphocytic choriomeningitis virus. J Immunol. 1999;163:6114–22.
pubmed: 10570301
doi: 10.4049/jimmunol.163.11.6114
Lykens JE, Terrell CE, Zoller EE, Risma K, Jordan MB. Perforin is a critical physiologic regulator of T-cell activation. Blood. 2011;118:618–26.
pubmed: 21606480
pmcid: 3142903
doi: 10.1182/blood-2010-12-324533
Sepulveda FE, et al. Polygenic mutations in the cytotoxicity pathway increase susceptibility to develop HLH immunopathology in mice. Blood. 2016;127:2113–21.
pubmed: 26864340
doi: 10.1182/blood-2015-12-688960
Jessen B, et al. Graded defects in cytotoxicity determine severity of Hemophagocytic Lymphohistiocytosis in humans and mice. Front Immunol. 2013;4:34–6.
doi: 10.3389/fimmu.2013.00448
Singh RK, et al. Distinct and opposing roles for Rab27a/Mlph/MyoVa and Rab27b/Munc13-4 in mast cell secretion. FEBS J. 2013;280:892–903.
pubmed: 23281710
doi: 10.1111/febs.12081
Chiossone L, et al. Protection from inflammatory organ damage in a murine model of Hemophagocytic Lymphohistiocytosis using treatment with IL-18 binding protein. Front Immunol. 2012;3:1–10.
doi: 10.3389/fimmu.2012.00239
Johnson TS, et al. Etoposide selectively ablates activated T cells to control the immunoregulatory disorder hemophagocytic lymphohistiocytosis. J Immunol. 2014;192:84–91.
pubmed: 24259502
doi: 10.4049/jimmunol.1302282
Booth C, Carmo M, Gaspar HB. Gene therapy for haemophagocytic lymphohistiocytosis. Curr Gene Ther. 2014;14:437–46.
pubmed: 25245087
doi: 10.2174/1566523214666140918112113