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Cell Mediators of Autoimmune Hepatitis and Their Therapeutic Implications

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Abstract

Autoimmune hepatitis is associated with interactive cell populations of the innate and adaptive immune systems, and these populations are amenable to therapeutic manipulation. The goals of this review are to describe the key cell populations implicated in autoimmune hepatitis and to identify investigational opportunities to develop cell-directed therapies for this disease. Studies cited in PubMed from 1972 to 2014 for autoimmune hepatitis, innate and adaptive immune systems, and therapeutic interventions were examined. Dendritic cells can promote immune tolerance to self-antigens, present neo-antigens that enhance the immune response, and expand the regulatory T cell population. Natural killer cells can secrete pro-inflammatory and anti-inflammatory cytokines and modulate the activity of dendritic cells and antigen-specific T lymphocytes. T helper 2 lymphocytes can inhibit the cytotoxic activities of T helper 1 lymphocytes and limit the expansion of T helper 17 lymphocytes. T helper 17 lymphocytes can promote inflammatory activity, and they can also up-regulate genes that protect against oxidative stress and hepatocyte apoptosis. Natural killer T cells can expand the regulatory T cell population; gamma delta lymphocytes can secrete interleukin-10, stimulate hepatic regeneration, and induce the apoptosis of hepatic stellate cells; and antigen-specific regulatory T cells can dampen immune cell proliferation and function. Pharmacological agents, neutralizing antibodies, and especially the adoptive transfer of antigen-specific regulatory T cells that have been freshly generated ex vivo are evolving as management strategies. The cells within the innate and adaptive immune systems are key contributors to the occurrence of autoimmune hepatitis, and they are attractive therapeutic targets.

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  1. Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada

    Aldo J. Montano-Loza

  2. Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN, 55905, USA

    Albert J. Czaja

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Montano-Loza, A.J., Czaja, A.J. Cell Mediators of Autoimmune Hepatitis and Their Therapeutic Implications. Dig Dis Sci 60, 1528–1542 (2015). https://doi.org/10.1007/s10620-014-3473-z

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