The physiological and pathophysiological role of iRhom-2

• Applicant: Professor Philipp Alexander Lang, Ph.D.
• Subject Area: Gastroenterology
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 221604464

• Final Report Year: 2015

Final Report Abstract

Taken together, the results of the research grant show in published and unpublished observations that iRhom2 has a critical role in several settings. Moreover, we could further our understanding of the molecular interaction and regulation of ADAM17 via iRhom2, but also iRhom1. Also, we observed an unidentified role of TNF-alpha during viral infection, which may be partially triggered by iRhom2. The preliminary observations all point to a predominant role of iRhom1, iRhom2, and TNF-alpha during liver damage (especially virally induced) and regeneration. Consequently, an extension of the research will be proposed as part of the Collaborative Research Center 974:”Kommunikation und Systemrelevanz bei Leberschädigung und Regeneration”.

Publications

• iRhom2 controls the substrate selectivity of stimulated ADAM17-dependent ectodomain shedding. Proc Natl Acad Sci USA. 2013 Jul 9;110(28):11433-8
  Maretzky T, McIlwain DR, Issuree PD, Li X, Malapeira J, Amin S, Lang PA, Mak TW, Blobel CP
  (See online at https://doi.org/10.1073/pnas.1302553110)
• Novel role for IRHOM2 in the pathogenesis of inflammatory arthritis. J Clin Invest. 2013 Feb 1;123(2):928-32
  Isuree PDA, Maretzky T, McIlwain DR, Monette S, Qing X, Lang PA, Swendeman SL, Park-Min KH, Binder N, Kalliolias GD, Yarilina A, Horiuchi K, Ivashkiv LB, Mak TW, Salomon JE, Blobel CP
  
• Reactive oxygen species delay control of lymphocytic choriomeningitis virus. Cell Death Differ. 2013 Apr;20(4):649-58
  Lang PA, Xu HC, Grusdat M, McIlwain DR, Pandyra AA, Harris IS, Shaabani N, Honke N, Kumar Maney S, Lang E, Pozdeev VI, Recher M, Odermatt B, Brenner D, Häussinger D, Ohashi PS, Hengartner H, Zinkernagel RM, Mak TW, Lang KS
  (See online at https://doi.org/10.1038/cdd.2012.167)
• IRF4 and BATF are critical for CD8+ T-cell function following infection with LCMV. Cell Death Differ. 2014 Feb 14
  Grusdat M, McIlwain DR, Xu HC, Pozdeev VI, Knievel J, Crome SQ, Robert-Tissot C, Dress RJ, Pandyra AA, Speiser DE, Lang E, Maney SK, Elford AR, Hamilton SR, Scheu S, Pfeffer K, Bode J, Mittrücker HW, Lohoff M, Huber M, Häussinger D, Ohashi PS, Mak TW, Lang KS, Lang PA
  (See online at https://doi.org/10.1038/cdd.2014.19)
• Type I interferon protects antiviral CD8(+) T cells from NK cell cytotoxicity. Immunity. 2014 Jun 19;40(6):949-60
  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
  (See online at https://doi.org/10.1016/j.immuni.2014.05.004)
• BAFFR deficiency results in limited CD169+ macrophage function during viral infection. J Virol. 2015 May;89(9):4748-59
  Xu HC, Huang J, Khairnar V, Duhan V, Pandyra AA, Grusdat M, Shinde P, McIlwain DR, Maney SK, Gommerman J, Löhning M, Ohashi PS, Mak TW, Pieper K, Sic H, Speletas M, Eibel H, Ware CF, Tumanov AV, Kruglov AA, Nedospasov SA, Häusinger D, Recher M, Lang KS, Lang PA
  (See online at https://doi.org/10.1128/JVI.02976-14)