Author | Sertorio, Mathieu | |
Author | Hou, Xunya | |
Author | Carmo, Rodrigo F | |
Author | Dessein, Hélia | |
Author | Cabantous, Sandrine | |
Author | Abdelwahed, Mohammed | |
Author | Romano, Audrey | |
Author | Albuquerque, Fernanda | |
Author | Vasconcelos, Luydson | |
Author | Carmo, Theomira Mauadie de Azevedo | |
Author | Li, Jun | |
Author | Varoquaux, Arthur | |
Author | Arnaud, Violaine | |
Author | Oliveira, Pablo | |
Author | Hamdoun, Anas | |
Author | He, Hongbin | |
Author | Adbelmaboud, Suzan | |
Author | Mergani, Adil | |
Author | Zhou, Jie | |
Author | Monis, Ahmed | |
Author | Pereira, Leila Beltrao | |
Author | Halfon, Philippe | |
Author | Bourlière, Marc | |
Author | Parana, Raymundo | |
Author | Reis, Mitermayer Galvão dos | |
Author | Gonnelli, David | |
Author | Moura, Patricia | |
Author | Elwali, Nasr Eldin | |
Author | Argiro, Laurent | |
Author | Li, Yuesheng | |
Author | Dessein, Alain | |
Access date | 2016-08-05T13:27:26Z | |
Available date | 2016-08-05T13:27:26Z | |
Document date | 2015 | |
Citation | SERTORIO, M. et al. IL-22 and IL-22 binding protein (IL-22BP) regulate fibrosis and cirrhosis in hepatitis C virus and schistosome infections. Hepatology, v. 61, p. 1321-1331, 2015. | pt_BR |
ISSN | 0270-9139 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/15197 | |
Language | eng | pt_BR |
Publisher | Wiley | pt_BR |
Rights | open access | pt_BR |
Title | IL-22 and IL-22 binding protein (IL-22BP) regulate fibrosis and cirrhosis in hepatitis C virus and schistosome infections | pt_BR |
Type | Article | pt_BR |
DOI | 10.1002/hep.27629 | |
Abstract | Interleukin (IL)-22 acts on epithelia, hepatocytes, and pancreatic cells and stimulates innate immunity, tissue protection, and repair. IL-22 may also cause inflammation and abnormal cell proliferation. The binding of IL-22 to its receptor is competed by IL-22 binding protein (IL-22BP), which may limit the deleterious effects of IL-22. The role of IL-22 and IL-22BP in chronic liver diseases is unknown. We addressed this question in individuals chronically infected with schistosomes or hepatitis C virus (HCV). We first demonstrate that schistosome eggs stimulate production of IL-22 transcripts and inhibit accumulation of IL22-BP transcripts in schistosome-infected mice, and that schistosome eggs selectively stimulate production of IL-22 in cultures of blood leukocytes from individuals chronically infected with Schistosoma japonicum. High IL-22 levels in cultures correlated with protection against hepatic fibrosis and portal hypertension. To test further the implication of IL-22/IL-22BP in hepatic disease, we analyzed common genetic variants of IL22RA2, which encodes IL-22BP, and found that the genotypes, AA, GG of rs6570136 (P = 0.003; odds ratio [OR] = 2), and CC, TT of rs2064501 (P = 0.01; OR = 2), were associated with severe fibrosis in Chinese infected with S. japonicum. We confirmed this result in Sudanese (rs6570136 GG [P = 0.0007; OR = 8.2], rs2064501 TT [P = 0.02; OR = 3.1]), and Brazilians (rs6570136 GG [P = 0.003; OR = 26], rs2064501 TC, TT (P = 0.03; OR = 11]) infected with S. mansoni. The aggravating genotypes were associated with high IL22RA2 transcripts levels. Furthermore, these same variants were also associated with HCV-induced fibrosis and cirrhosis (rs6570136 GG, GA [P = 0.007; OR = 1.7], rs2064501 TT, TC (P = 0.004; OR = 2.4]). Conclusions:
These results provide strong evidence that IL-22 protects against and IL-22BP aggravates
liver fibrosis and cirrhosis in humans with chronic liver infections. Thus, pharmacological
modulation of IL-22 BP may be an effective strategy to limit cirrhosis. | pt_BR |
Affilliation | Aix-Marseille Universit e. Marseille, France / Inserm. Marseille, France | pt_BR |
Affilliation | Hunan Institute of Parasitic Diseases. Hua-Ban Qiao Road Yueyang. China | pt_BR |
Affilliation | Universidade Federal do Vale do São Francisco. Petrolina, Brasil | pt_BR |
Affilliation | Aix-Marseille Universit e. Marseille, France / Inserm. Marseille, France | pt_BR |
Affilliation | Aix-Marseille Universit e. Marseille, France / Inserm. Marseille, France | pt_BR |
Affilliation | Institute of Nuclear Medicine. Wad Medani, Sudan | pt_BR |
Affilliation | Aix-Marseille Universit e. Marseille, France / Inserm. Marseille, France | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Instituto do Figado. Recife, PE, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Hunan Institute of Parasitic Diseases. Hua-Ban Qiao Road Yueyang. China | pt_BR |
Affilliation | APHM. CHU Timone, Radiology. Marseille, France | pt_BR |
Affilliation | Aix-Marseille Universit e. Marseille, France / Inserm. Marseille, France | pt_BR |
Affilliation | Aix-Marseille Universit e. Marseille, France / Inserm. Marseille, France / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Institute of Nuclear Medicine. Wad Medani, Sudan | pt_BR |
Affilliation | Hunan Institute of Parasitic Diseases. Hua-Ban Qiao Road Yueyang. China | pt_BR |
Affilliation | Institute of Nuclear Medicine. Wad Medani, Sudan | pt_BR |
Affilliation | Taif University. College of Applied Medical Sciences. Turabah, Saudi Arabia | pt_BR |
Affilliation | Institute of Nuclear Medicine. Wad Medani, Sudan | pt_BR |
Affilliation | Institute of Nuclear Medicine. Wad Medani, Sudan | pt_BR |
Affilliation | Instituto do Figado. Recife, PE, Brasil | pt_BR |
Affilliation | Hôpital Europeen. Virology Department. Marseille, France | pt_BR |
Affilliation | Hôpital Saint-Joseph. Hepatology Department. Marseille, France | pt_BR |
Affilliation | Federal University of Bahia. Faculty of Medicine. Department of Medicine. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | APHM. La Conception, Chirurgie plastique et reconstructrice. Marseille, France | pt_BR |
Affilliation | Universidade Pernambuco. Instituto de Ciencias Biologicas. Recife, PE, Brasil | pt_BR |
Affilliation | Institute of Nuclear Medicine. Wad Medani, Sudan | pt_BR |
Affilliation | Aix-Marseille Universite. Marseille, France / Inserm. Marseille, France | pt_BR |
Affilliation | Hunan Institute of Parasitic Diseases. Hua-Ban Qiao Road Yueyang. China | pt_BR |
Affilliation | Aix-Marseille Universite. Marseille, France / Inserm. Marseille, France / APHM. CHU Timone. Marseille, France | pt_BR |
Subject | Hepatitis C | pt_BR |
Subject | Interleukins | pt_BR |
Subject | Liver cirrhosis | pt_BR |
Subject | Adult | pt_BR |
Subject | Humans | pt_BR |
Subject | Schistosomiasis | pt_BR |
Subject | Receptors, interleukin | pt_BR |