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. 2011 Jan 27;3(1):1-7.
doi: 10.4254/wjh.v3.i1.1.

Genetic susceptibility to autoimmune liver disease

Jochen Mattner  1
Affiliations

Genetic susceptibility to autoimmune liver disease

Jochen Mattner. World J Hepatol. .

Abstract

Autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are considered as putative autoimmune diseases of the liver. Whereas strong evidence that bacterial infection may trigger PBC exists, the etiologies for PSC and AIH remain unknown. Although there have been significant discoveries of genetic polymorphisms that may underlie the susceptibility to these liver diseases, their associations with environmental triggers and the subsequent implications have been difficult to elucidate. While single nucleotide polymorphisms within the negative costimulatory molecule cytotoxic T lymphocyte antigen 4 (CTLA-4) have been suggested as genetic susceptibility factors for all three disorders, we discuss the implications of CTLA-4 susceptibility alleles mainly in the context of PBC, where Novosphingobium aromaticivorans, an ubiquitous alphaproteobacterium, has recently been specifically associated with the pathogenesis of this devastating liver disease. Ultimately, the discovery of infectious triggers of PBC may expand the concept of genetic susceptibility in immune-mediated liver diseases from the concept of aberrant immune responses against self-antigens to insufficient and/or inappropriate immunological defense mechanisms allowing microbes to cross natural barriers, establish infection and damage respective target organs.

Keywords: Diabetes; Natural killer T cells, Cytotoxic T lymphocyte antigen 4; Non-obese diabetic congenic mice; Novosphingobium; Primary biliary cirrhosis; Susceptibility loci.

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Figures

Figure 1
Figure 1
Regulation of T cell activation by cytotoxic T lymphocyte antigen 4. While cytotoxic T lymphocyte antigen 4 (CTLA-4) is constitutively expressed on regulatory T cells (Tregs), its expression is induced on effector T cells (Teff) upon activation. While it is well-established that CTLA-4 is required for the optimal function of Tregs, its role on natural killer T cells or effector T cells is less clear. DCs: dentritic cells; NKT: natural killer T; GSLs: glycosphingolipids.
See this image and copyright information in PMC

References

    1. Gao B, Jeong WI, Tian Z. Liver: An organ with predominant innate immunity. Hepatology. 2008;47:729–736. - PubMed
    1. Seki S, Habu Y, Kawamura T, Takeda K, Dobashi H, Ohkawa T, Hiraide H. The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK) cells and NK1.1 Ag+ T cells in T helper 1 immune responses. Immunol Rev. 2000;174:35–46. - PubMed
    1. Benseler V, McCaughan GW, Schlitt HJ, Bishop GA, Bowen DG, Bertolino P. The liver: a special case in transplantation tolerance. Semin Liver Dis. 2007;27:194–213. - PubMed
    1. Selmi C, Mackay IR, Gershwin ME. The immunological milieu of the liver. Semin Liver Dis. 2007;27:129–139. - PubMed
    1. Malnick S, Melzer E, Sokolowski N, Basevitz A. The involvement of the liver in systemic diseases. J Clin Gastroenterol. 2008;42:69–80. - PubMed