Effects of a Small-Molecule Perforin Inhibitor in a Mouse Model of CD8 T Cell-Mediated Neuroinflammation.

Mice Animals Perforin Neuroinflammatory Diseases Malaria, Cerebral Endothelial Cells Susac Syndrome Mice, Knockout CD8-Positive T-Lymphocytes Disease Models, Animal

Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
07 2023
Historique:
received: 01 08 2022
accepted: 21 02 2023
medline: 24 4 2023
pubmed: 21 4 2023
entrez: 20 04 2023
Statut: epublish

Résumé

Alteration of the blood-brain barrier (BBB) at the interface between blood and CNS parenchyma is prominent in most neuroinflammatory diseases. In several neurologic diseases, including cerebral malaria and Susac syndrome, a CD8 T cell-mediated targeting of endothelial cells of the BBB (BBB-ECs) has been implicated in pathogenesis. In this study, we used an experimental mouse model to evaluate the ability of a small-molecule perforin inhibitor to prevent neuroinflammation resulting from cytotoxic CD8 T cell-mediated damage of BBB-ECs. Using an in vitro coculture system, we first identified perforin as an essential molecule for killing of BBB-ECs by CD8 T cells. We then found that short-term pharmacologic inhibition of perforin commencing after disease onset restored motor function and inhibited the neuropathology. Perforin inhibition resulted in preserved BBB-EC viability, maintenance of the BBB, and reduced CD8 T-cell accumulation in the brain and retina. Therefore, perforin-dependent cytotoxicity plays a key role in the death of BBB-ECs inflicted by autoreactive CD8 T cells in a preclinical model and potentially represents a therapeutic target for CD8 T cell-mediated neuroinflammatory diseases, such as cerebral malaria and Susac syndrome.

Sections du résumé

BACKGROUND AND OBJECTIVES
Alteration of the blood-brain barrier (BBB) at the interface between blood and CNS parenchyma is prominent in most neuroinflammatory diseases. In several neurologic diseases, including cerebral malaria and Susac syndrome, a CD8 T cell-mediated targeting of endothelial cells of the BBB (BBB-ECs) has been implicated in pathogenesis.
METHODS
In this study, we used an experimental mouse model to evaluate the ability of a small-molecule perforin inhibitor to prevent neuroinflammation resulting from cytotoxic CD8 T cell-mediated damage of BBB-ECs.
RESULTS
Using an in vitro coculture system, we first identified perforin as an essential molecule for killing of BBB-ECs by CD8 T cells. We then found that short-term pharmacologic inhibition of perforin commencing after disease onset restored motor function and inhibited the neuropathology. Perforin inhibition resulted in preserved BBB-EC viability, maintenance of the BBB, and reduced CD8 T-cell accumulation in the brain and retina.
DISCUSSION
Therefore, perforin-dependent cytotoxicity plays a key role in the death of BBB-ECs inflicted by autoreactive CD8 T cells in a preclinical model and potentially represents a therapeutic target for CD8 T cell-mediated neuroinflammatory diseases, such as cerebral malaria and Susac syndrome.

Identifiants

DOI: 10.1212/NXI.0000000000200117 PMID: 37080596 PMC: PMC10119812
pubmed: 37080596
pii: 10/4/e200117
doi: 10.1212/NXI.0000000000200117
pmc: PMC10119812
pii:
doi:

Substances chimiques

Perforin 126465-35-8

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Austrian Science Fund FWF
ID : P 34864
Pays : Austria
Organisme : Wellcome Trust
Pays : United Kingdom

Informations de copyright

Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.

Références

J Exp Med. 2007 Sep 3;204(9):2023-30
pubmed: 17682068
Tissue Barriers. 2021 Jul 3;9(3):1926190
pubmed: 34152937
Lab Invest. 2005 Jun;85(6):734-46
pubmed: 15908914
Nat Rev Immunol. 2015 Jun;15(6):388-400
pubmed: 25998963
PLoS One. 2013;8(1):e52586
pubmed: 23320074
Nat Neurosci. 2019 Nov;22(11):1892-1902
pubmed: 31611708
Brain. 2022 Apr 29;145(3):858-871
pubmed: 35136969
J Exp Med. 2011 Dec 19;208(13):2615-23
pubmed: 22143887
ACS Pharmacol Transl Sci. 2022 May 31;5(6):429-439
pubmed: 35711815
Nat Commun. 2018 Nov 15;9(1):4805
pubmed: 30442932
J Exp Med. 2000 Aug 7;192(3):393-404
pubmed: 10934227
Front Endocrinol (Lausanne). 2021 Jan 05;11:606434
pubmed: 33469446
Nat Neurosci. 2018 Oct;21(10):1380-1391
pubmed: 30224810
Brain. 2018 Jul 1;141(7):2066-2082
pubmed: 29873694
Methods Mol Biol. 2016;1304:211-29
pubmed: 25520281
Cell. 2020 Feb 20;180(4):764-779.e20
pubmed: 32059779
Semin Immunopathol. 2015 May;37(3):221-31
pubmed: 25772948
Int J Mol Sci. 2022 Feb 06;23(3):
pubmed: 35163755
Elife. 2016 Jun 23;5:
pubmed: 27336724
Cell. 1994 Jan 14;76(1):17-27
pubmed: 8287475
Eur J Immunol. 2015 Apr;45(4):1043-58
pubmed: 25545837
Blood. 2013 Apr 4;121(14):2659-68
pubmed: 23377437
PLoS One. 2016 Mar 04;11(3):e0150945
pubmed: 26942913
J Clin Invest. 2019 Nov 1;129(11):4758-4768
pubmed: 31566584
Methods Enzymol. 2019;629:291-306
pubmed: 31727246
Brain. 2012 May;135(Pt 5):1622-38
pubmed: 22539258
Sci Adv. 2022 Feb 11;8(6):eabk3147
pubmed: 35148176
Immunity. 2003 Mar;18(3):319-29
pubmed: 12648450
Vasc Biol. 2020 Mar 20;2(1):H1-H18
pubmed: 32923970
Ann Neurol. 2012 Nov;72(5):648-72
pubmed: 23280789
Neurochem Res. 2013 Nov;38(11):2295-304
pubmed: 23990225
Oncoimmunology. 2013 Dec 1;2(12):e27384
pubmed: 24501693
Science. 1999 Dec 3;286(5446):1957-9
pubmed: 10583959
Front Immunol. 2020 Jun 02;11:991
pubmed: 32655545
Eur J Immunol. 2016 Sep;46(9):2187-203
pubmed: 27338806
J Clin Invest. 2020 Mar 2;130(3):1128-1138
pubmed: 31821175
J Autoimmun. 1990 Jun;3(3):247-55
pubmed: 2397018
Nature. 2017 Jun 29;546(7660):656-661
pubmed: 28636593
J Immunol. 2004 Apr 15;172(8):5120-7
pubmed: 15067096
Lancet Neurol. 2015 Sep;14(9):945-55
pubmed: 26293566
Sci Transl Med. 2022 Apr 13;14(640):eabl6058
pubmed: 35417190
J Immunol. 2010 Oct 15;185(8):4846-55
pubmed: 20861356
J Immunol. 2008 Oct 1;181(7):4918-25
pubmed: 18802095
Cell Mol Immunol. 2009 Feb;6(1):15-25
pubmed: 19254476
Sci Transl Med. 2022 Apr 13;14(640):eabl6157
pubmed: 35417189
Front Immunol. 2021 Jul 15;12:707972
pubmed: 34335623
Nature. 2020 Jan;577(7790):399-404
pubmed: 31915375
J Immunol. 2008 Aug 1;181(3):1617-21
pubmed: 18641296
Acta Neuropathol. 2018 Mar;135(3):311-336
pubmed: 29411111
Nat Commun. 2019 Dec 18;10(1):5779
pubmed: 31852955
Nature. 1994 May 5;369(6475):31-7
pubmed: 8164737
Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11270-5
pubmed: 18678898
Brain. 2020 Dec 1;143(12):3717-3733
pubmed: 33118032
PLoS Pathog. 2015 Jun 05;11(6):e1004963
pubmed: 26046849
Bioorg Med Chem Lett. 2017 Feb 15;27(4):1050-1054
pubmed: 28110869
Circ Heart Fail. 2021 Oct;14(10):e007982
pubmed: 34555935
PLoS Pathog. 2016 Dec 1;12(12):e1006022
pubmed: 27907215
Malar J. 2013 Jul 26;12:260
pubmed: 23890318
Nature. 2009 Nov 5;462(7269):94-8
pubmed: 19829296
J Exp Med. 2005 Jun 6;201(11):1805-14
pubmed: 15939794
J Med Chem. 2022 Nov 10;65(21):14305-14325
pubmed: 36263926

Auteurs

Carmen Gonzalez-Fierro (C)

From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France.

Coralie Fonte (C)

From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France.

Eloïse Dufourd (E)

From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France.

Vincent Cazaentre (V)

From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France.

Sidar Aydin (S)

From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France.

Britta Engelhardt (B)

From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France.

Rachel R Caspi (RR)

From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France.

Biying Xu (B)

From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France.

Guillaume Martin-Blondel (G)

From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France.

Julie A Spicer (JA)

From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France.

Joseph A Trapani (JA)

From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France.

Jan Bauer (J)

From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France.

Roland S Liblau (RS)

From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France. roland.liblau@inserm.fr.

Chloé Bost (C)

From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Effects of a Small-Molecule Perforin Inhibitor...
questionsmedicales.fr › Eucaryotes › Animaux › Effects of a Small-Molecule Perforin Inhibitor...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Perforines › Perforine › Effects of a Small-Molecule Perforin Inhibitor...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Maladies neuro-inflammatoires › Effects of a Small-Molecule Perforin Inhibitor...
questionsmedicales.fr › Maladies du système nerveux › Maladies du système nerveux central › Infections du système nerveux central › Infections parasitaires du système nerveux central › Protozooses du système nerveux central › Paludisme cérébral › Effects of a Small-Molecule Perforin Inhibitor...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules endothéliales › Effects of a Small-Molecule Perforin Inhibitor...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Syndrome de Susac › Effects of a Small-Molecule Perforin Inhibitor...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Effects of a Small-Molecule Perforin Inhibitor...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › Effects of a Small-Molecule Perforin Inhibitor...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Effects of a Small-Molecule Perforin Inhibitor...