Recent insights into the role of the PD-1/PD-L1 pathway in immunological tolerance and autoimmunity

Elena Gianchecchi, Domenico Vittorio Delfino, Alessandra Fierabracci

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1091-1100
Number of pages10
JournalAutoimmunity Reviews
Issue number11
Publication statusPublished - Sep 2013


  • Autoimmunity etiopathogenesis
  • B lymphocytes
  • Candidate autoimmune genes
  • Prevention-treatment
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy


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