TY - JOUR
T1 - Regulatory T cells in autoimmune hepatitis
T2 - Un updated overview
AU - Longhi, Maria Serena
AU - Mieli-Vergani, Giorgina
AU - Vergani, Diego
N1 - Funding Information:
MSL is supported by the National Institutes of Health ( R01 DK108894 and R01 DK124408 ) and by the Seed Grant Award (Department of Anesthesia, Critical Care and Pain Medicine, BIDMC) .
Publisher Copyright:
© 2021 Elsevier Ltd
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5
Y1 - 2021/5
N2 - Regulatory T-cells (Tregs) are key players in the maintenance of immune homeostasis by preventing immune responses to self-antigens. Defects in Treg frequency and/or function result in overwhelming CD4 and CD8 T cell immune responses participating in the autoimmune attack. Perpetuation of autoimmune damage is also favored by Treg predisposition to acquire effector cell features upon exposure to a proinflammatory challenge. Treg impairment plays a permissive role in the initiation and perpetuation of autoimmune liver diseases, namely autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. In this Review, we outline studies reporting the role of Treg impairment in the pathogenesis of these conditions and discuss methods to restore Treg number and function either by generation/expansion in the test tube or through in vivo expansion upon administration of low dose IL-2. Challenges and caveats of these potential therapeutic strategies are also reviewed and discussed.
AB - Regulatory T-cells (Tregs) are key players in the maintenance of immune homeostasis by preventing immune responses to self-antigens. Defects in Treg frequency and/or function result in overwhelming CD4 and CD8 T cell immune responses participating in the autoimmune attack. Perpetuation of autoimmune damage is also favored by Treg predisposition to acquire effector cell features upon exposure to a proinflammatory challenge. Treg impairment plays a permissive role in the initiation and perpetuation of autoimmune liver diseases, namely autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. In this Review, we outline studies reporting the role of Treg impairment in the pathogenesis of these conditions and discuss methods to restore Treg number and function either by generation/expansion in the test tube or through in vivo expansion upon administration of low dose IL-2. Challenges and caveats of these potential therapeutic strategies are also reviewed and discussed.
KW - Autoimmune hepatitis
KW - Effector lymphocytes
KW - Immune tolerance
KW - Immunotherapy
KW - Regulatory T cells
UR - http://www.scopus.com/inward/record.url?scp=85101595413&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2021.102619
DO - 10.1016/j.jaut.2021.102619
M3 - Review article
AN - SCOPUS:85101595413
SN - 0896-8411
VL - 119
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
M1 - 102619
ER -
