title: Recent insights into the role of the PD-1/PD-L1 pathway in immunological tolerance and autoimmunity.
abstract: Autoimmune diseases represent a heterogeneous group of conditions whose incidence is increasing worldwide. This has stimulated studies on their etiopathogenesis, derived from a complex interaction between genetic and environmental factors, in order to improve prevention and treatment of these disorders. The relevance of T regulatory cells and of the PD-1/PD-L1 pathway in controlling immune responses has been highlighted. Recent studies have in particular elucidated the putative role of the PD-1/PD-L1 pathway in regulating T cell responses and its effects on immunological tolerance and immune-mediated tissue damage. The role of the PD-1/PD-L1 pathway in autoimmunity has been already investigated in vivo in several experimental animal models including insulin-dependent diabetes mellitus, systemic lupus erythematosus, myocarditis, encephalomyelitis, rheumatoid arthritis and inflammatory bowel diseases. With the advent of candidate gene and genome-wide association studies, single nucleotide polymorphisms (SNPs) in PD-1 gene in humans have demonstrated relevant associations with a higher risk of developing autoimmune diseases in certain ethnic groups. In this review we present recent insights into the role of the PD-1/PD-L1 pathway in regulating lymphocyte activation, promotion of T regulatory cell development and function, breakdown of tolerance and development of autoimmunity. We finally speculate on the possible development of novel therapeutic treatments in human autoimmunity by modulating the PD-1/PD-L1 pathway.
authors.affiliation: Autoimmunity Laboratory, Immunology Area, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gianchecchi
authors.forename: Domenico Vittorio
authors.initials: DV
authors.lastname: Delfino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fierabracci
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D060890:B7-H1 Antigen / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Autoimmunity etiopathogenesis; B lymphocytes; Candidate autoimmune genes; Prevention-treatment; T lymphocytes