C8 - IL-22 and IL-22BP in liver regeneration and carcinogenesis
Prof. Dr. med. Samuel Huber
I. Medizinische Klinik und Poliklinik
Interleukin 22 (IL-22) is a pleiotropic cytokine, which may have protective and pathogenic properties depending on the environment. It particularly plays a role during regeneration, infection, and carcinogenesis. Normally, IL-22 binds to the membrane-bound IL-22 receptor (IL-22r1) thereby exerting its activities. However, there is also a soluble IL-22 receptor, the IL-22 binding protein (IL-22BP), which binds and neutralizes IL-22.
IL-22 seems to play a protective role during liver regeneration. However, uncontrolled IL-22 activity might promote liver cancer.
C8 in 60 SecondsVideoarchivonline seit 17.03.2014
Our previous findings have shown that IL-22BP plays a crucial role in controlling the activity of IL-22 during wound healing and carcinogenesis. Now we aim to identify the cellular source of IL-22 and IL-22BP in the liver. Furthermore, we are interested in the pathways regulating IL-22 and IL-22BP production. Finally, we want to investigate the interaction between IL-22 and IL-22BP and how this controls liver regeneration and carcinogenesis.
Our long-term aim is to identify new therapeutic strategies that, on the one hand, promote liver regeneration and, on the other hand, inhibit liver carcinogenesis.
Sellau J, Alvarado CF, Hoenow S, Mackroth MS, Kleinschmidt D, Huber S, Jacobs T
IL-22 dampens the T cell response in experimental malaria
Sci Rep. 2016 Jun 17;6:28058. doi: 10.1038/srep28058.
Pelczar P, Witkowski M, Perez LG, Kempski J, Hammel AG, Brockmann L, Kleinschmidt D, Wende S, Haueis C, Bedke T, Witkowski M, Krasemann S, Steurer S, Booth CJ, Busch P, König A, Rauch U, Benten D, Izbicki JR, Rösch T, Lohse AW, Strowig T, Gagliani N, Flavell RA, Huber S
A pathogenic role for T cell-derived IL-22BP in inflammatory bowel disease
Science. 2016 Oct 21;354(6310):358362
Gagliani N, Hu B, Huber S, Elinav E, Flavell RA
The fire within: microbes inflame tumors
Cell. 2014 May 8;157(4):776-83. doi: 10.1016/j.cell.2014.03.006
IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine.
Huber S, Gagliani N, Zenewicz LA, Huber FJ, Bosurgi L, Hu B, Hedl M, Zhang W, O’Connor W Jr, Murphy AJ, Valenzuela DM, Yancopoulos GD, Booth CJ, Cho JH, Ouyang W, Abraham C, Flavell RA.
Nature. 2012 Nov 8;491(7423):259-63. doi: 10.1038/nature11535. Epub 2012 Oct 17.