Dr. Johannes Hofer
MedUni Wien RESEARCHER OF THE MONTH, August 2017
Complement regulation leads to the generation of complement split products such as complement component (C)4d, a marker for disease activity in autoimmune syndromes or antibody-mediated allograft rejection. However, the physiologic role of C4d has been unknown. The present study identifies Ig-like transcript (ILT)4 and ILT5v2 as cellular receptors for C4d.
Both receptors, expressed on monocytes, macrophages and dendritic cells, also interacted with complement split products C3d, C4b, C3b and iC3b. However, C4d did not bind to classic complement receptors. In monocytes, C4d exerted a dose-dependent inhibition of pro-inflammatory cytokine secretion as well as an attenuation of intracellular Ca2+ flux. Cell surface-resident ILT4 conferred endocytosis of soluble monomeric C4d.
Selected literature
- Kovarik J., Kernbauer E, Hölzl MA, Hofer J, Gualdoni GA, Schmetterer KG, Miftari F, Sobanov Y, Meshcheryakova A, Mechtcheriakova D, Witzeneder N, Greiner G, Repic A, Waidhofer-Söllner P, Saemann MD, Decker T, Zlabinger GJ. Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis. (Accepted for publication in PLOS ONE).
- Hofer J, Forster F, Isenman DE, Wahrmann M, Leitner J, Hölzl MA, Kovarik JJ, Stockinger H, Böhmig GA, Steinberger P, Zlabinger GJ. Ig-like transcript 4 as a cellular receptor for soluble complement fragment C4d. FASEB J. 2016 Apr;30(4):1492-503.
- Hofer J, Regele H, Böhmig GA, Gutjahr G, Kikić Z, Mühlbacher F, Kletzmayr J. Pre-implant biopsy predicts outcome of single-kidney transplantation independent of clinical donor variables. Transplantion. 2014 Feb 27;97(4):426-32
- Gualdoni GA, Kovarik JJ, Hofer J, Dose F, Pignitter M, Doberer D, Steinberger P, Somoza V, Wolzt M, Zlabinger GJ. Resveratrol enhances TNF-α production in human monocytes upon bacterial stimulation. Biochim Biophys Acta. 2014 Jan;1840(1):95-105.
- Kovarik JJ, Hölzl MA, Hofer J, Waidhofer-Söllner P, Sobanov J, Koeffel R, Saemann MD, Mechtcheriakova D, Zlabinger GJ. Eicosanoid modulation by the short chain fatty acid n-butyrate in human monocytes. Immunology. 2013 Jul;139(3):395-405
- Hölzl MA, Hofer J, Kovarik JJ, Roggenbuck D, Reinhold D, Goihl A, Gärtner M, Steinberger P, Zlabinger GJ. The zymogen granule protein 2 (GP2) binds to scavenger receptor expressed on endothelial cells I (SREC-I). Cell Immunol. 2011;267(2):88-93
- Kovarik JJ, Tillinger W, Hofer J, Hölzl MA, Heinzl H, Saemann MD, Zlabinger GJ. Impaired anti-inflammatory efficacy of n-butyrate in patients with IBD. Eur J Clin Invest. 2011 Mar;41(3):291-8
- Hölzl MA, Gärtner M, Kovarik JJ, Hofer J, Bernheimer H, Sunder-Plassmann G, Zlabinger GJ. Quantification of α-galactosidase activity in intact leukocytes. Clin Chim Acta. 2010 Nov 11;411(21-22):1666-70
- Koppelstaetter C, Schratzberger G, Perco P, Hofer J, Mark W, Ollinger R, Oberbauer R, Schwarz C, Mitterbauer C, Kainz A, Karkoszka H, Wiecek A, Mayer B, Mayer G. Markers of cellular senescence in zero hour biopsies predict outcome in renal transplantation. Aging Cell. 2008 Aug;7(4):491-7
- Hölzl MA, Hofer J, Steinberger P, Pfistershammer K, Zlabinger GJ. Host antimicrobial proteins as endogenous immunomodulators. Immunol Lett. 2008 Aug 15;119(1-2):4-11
* International Patent Application: “Complement split product C4d for the treatment of inflammatory conditions”. Int. Appl. No: PCT/EP2013/063973. Int. Filing Date: 02.07.2013; Pub. Date: 09.01.2014 (Pub. No: WO2014006063)