Type I Interferon protects anti-viral T cells from NK cell mediated killing.

NK cells can limit anti-viral Type I interferon receptor deficient T cells. This mechanism is critical for productive adaptive immunity. 

Xu et al. Immunity. 2014.

The protein iRhom2 triggers TNF-alpha secretion

The protein iRhom2 is involved in maturation of the TNF-alpha converting enzyme (TACE). Absence of iRhom2 results into reduced TACE activity thus reduced soluble TNF-alpha production.  

McIlwain et al. Science. 2012.

Enforced Viral Replication is critical for functional anti-viral immunity

The mechanism "enforced viral replication" describes the active amplification of viral particles in spleen tissue to guarantee sufficient antigen for adaptive immune priming. Absence of enforced viral replication results into impaired anti-viral immunity and fatal disease. 

Honke et al. Nat Immunol. 2011.

Selected Publications

Date: February 2021


Zhuang Y, Xu HC, Shinde PV, Warfsmann J, Vasilevska J, Sundaram B, Behnke K, Huang J, Hoell JI, Borkhardt A, Pfeffer K, Taha MS, Herebian D, Mayatepek E, Brenner D, Ahmadian MR, Keitel V, Wieczorek D, Häussinger D, Pandyra AA, Lang KS, Lang PA. Fragile X mental retardation protein protects against tumour necrosis factor-mediated cell death and liver injury. Gut. 2020 Jan;69(1):133-145.

Baazim H, Schweiger M, Moschinger M, Xu H, Scherer T, Popa A, Gallage S, Ali A, Khamina K, Kosack L, Vilagos B, Smyth M, Lercher A, Friske J, Merkler D, Aderem A, Helbich TH, Heikenwälder M, Lang PA, Zechner R, Bergthaler A. CD8+ T cells induce cachexia during chronic viral infection.Nat Immunol. 2019 Jun;20(6):701-710

Behnke K, Zhuang Y, Xu HC, Sundaram B, Reich M, Shinde PV, Huang J, Modares NF, Tumanov AV, Polz R, Scheller J, Ware CF, Pfeffer K, Keitel V, Häussinger D, Pandyra AA, Lang KS, Lang PA. B Cell-Mediated Maintenance of Cluster of Differentiation 169-Positive Cells Is Critical for Liver Regeneration.Hepatology. 2018 May 9.

Delacher M, Imbusch CD, Weichenhan D, Breiling A, Hotz-Wagenblatt A, Träger U, Hofer AC, Kägebein D, Wang Q, Frauhammer F, Mallm JP, Bauer K, Herrmann C, Lang PA, Brors B, Plass C, Feuerer M. Genome-wide DNA-methylation landscape defines specialization of regulatory T cells in tissues.Nat Immunol. 2017 Oct;18(10):1160-1172.

Mak TW, Grusdat M, Duncan GS, Dostert C, Nonnenmacher Y, Cox M, Binsfeld C, Hao Z, Brüstle A, Itsumi M, Jäger C, Chen Y, Pinkenburg O, Camara B, Ollert M, Bindslev-Jensen C, Vasiliou V, Gorrini C, Lang PA, Lohoff M, Harris IS, Hiller K, Brenner D. Glutathione Primes T Cell Metabolism for Inflammation.Immunity. 2017 Apr 18;46(4):675-689.

Beyer M, Abdullah Z, Chemnitz JM, Maisel D, Sander J, Lehmann C, Thabet Y, Shinde PV, Schmidleithner L, Köhne M, Trebicka J, Schierwagen R, Hofmann A, Popov A, Lang KS, Oxenius A, Buch T, Kurts C, Heikenwalder M, Fätkenheuer G, Lang PA, Hartmann P, Knolle PA, Schultze JL. Tumor-necrosis factor impairs CD4(+) T cell-mediated immunological control in chronic viral infection.Nat Immunol. 2016 May;17(5):593-603.

Bhattacharya A, Hegazy AN, Deigendesch N, Kosack L, Cupovic J, Kandasamy RK, Hildebrandt A, Merkler D, Kühl AA, Vilagos B, Schliehe C, Panse I, Khamina K, Baazim H, Arnold I, Flatz L, Xu HC, Lang PA, Aderem A, Takaoka A, Superti-Furga G, Colinge J, Ludewig B, Löhning M, Bergthaler A. Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage.Immunity. 2015 Nov 17;43(5):974-86.

Xu HC, Grusdat M, Pandyra AA, Polz R, Huang J, Sharma P, Deenen R, Köhrer K, Rahbar R, Diefenbach A, Gibbert K, Löhning M, Höcker L, Waibler Z, Häussinger D, Mak TW, Ohashi PS, Lang KS, Lang PA. Type I interferon protects antiviral CD8+ T cells from NK cell cytotoxicity. Immunity. 2014 Jun 19;40(6):949-60.

Lang E, Gatidis S, Freise NF, Bock H, Kubitz R, Lauermann C, Orth HM, Klindt C, Schuier M, Keitel V, Reich M, Liu G, Schmidt S, Xu HC, Qadri SM, Herebian D, Pandyra AA, Mayatepek E, Gulbins E, Lang F, Häussinger D, Lang KS, Föller M, Lang PA. Conjugated bilirubin triggers anemia by inducing erythrocyte death. Hepatology. 2014 Jul 28. doi: 10.

McIlwain DR, Lang PA, Maretzky T, Hamada K, Ohishi K, Maney SK, Berger T, Murthy A, Duncan G, Xu HC, Lang KS, Häussinger D, Wakeham A, Itie-Youten A, Khokha R, Ohashi PS, Blobel CP, Mak TW. iRhom2 regulation of TACE controls TNF-mediated protection against Listeria and responses to LPS. Science. 2012 Jan 13;335(6065):229-32. 

Lang PA, Lang KS, Xu HC, Grusdat M, Parish IA, Recher M, Elford AR, Dhanji S, Shaabani N, Tran CW, Dissanayake D, Rahbar R, Ghazarian M, Brüstle A, Fine J, Chen P, Weaver CT, Klose C, Diefenbach A, Häussinger D, Carlyle JR, Kaech SM, Mak TW, Ohashi PS. Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8+ T-cell immunity. Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1210-5.

Honke N, Shaabani N, Cadeddu G, Sorg UR, Zhang DE, Trilling M, Klingel K, Sauter M, Kandolf R, Gailus N, van Rooijen N, Burkart C, Baldus SE, Grusdat M, Löhning M, Hengel H, Pfeffer K, Tanaka M, Häussinger D, Recher M, Lang PA, Lang KS. Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus. Nat Immunol. 2011 Nov 20;13(1):51-7.

Pellegrini M, Calzascia T, Toe JG, Preston SP, Lin AE, Elford AR, Shahinian A, Lang PA, Lang KS, Morre M, Assouline B, Lahl K, Sparwasser T, Tedder TF, Paik JH, DePinho RA, Basta S, Ohashi PS, Mak TW. IL-7 engages multiple mechanisms to overcome chronic viral infection and limit organ pathology. Cell. 2011 Feb 18;144(4):601-13.

Lang PA, Contaldo C, Georgiev P, El-Badry AM, Recher M, Kurrer M, Cervantes-Barragan L, Ludewig B, Calzascia T, Bolinger B, Merkler D, Odermatt B, Bader M, Graf R, Clavien PA, Hegazy AN, Löhning M, Harris NL, Ohashi PS, Hengartner H, Zinkernagel RM, Lang KS. Aggravation of viral hepatitis by platelet-derived serotonin. Nat Med. 2008 Jul;14(7):756-61. 

Recher M, Lang KS, Navarini A, Hunziker L, Lang PA, Fink K, Freigang S, Georgiev P, Hangartner L, Zellweger R, Bergthaler A, Hegazy AN, Eschli B, Theocharides A, Jeker LT, Merkler D, Odermatt B, Hersberger M, Hengartner H, Zinkernagel RM. Extralymphatic virus sanctuaries as a consequence of potent T-cell activation. Nat Med. 2007 Nov;13(11):1316-23.

Junt T, Moseman EA, Iannacone M, Massberg S, Lang PA, Boes M, Fink K, Henrickson SE, Shayakhmetov DM, Di Paolo NC, van Rooijen N, Mempel TR, Whelan SP, von Andrian UH. Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature. 2007 Nov 1;450(7166):110-4.

Lang PA, Schenck M, Nicolay JP, Becker JU, Kempe DS, Lupescu A, Koka S, Eisele K, Klarl BA, Rübben H, Schmid KW, Mann K, Hildenbrand S, Hefter H, Huber SM, Wieder T, Erhardt A, Häussinger D, Gulbins E, Lang F. Liver cell death and anemia in Wilson disease involve acid sphingomyelinase and ceramide. Nat Med. 2007 Feb;13(2):164-70.

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