Role of PD-L1 in Gut Mucosa Tolerance and Chronic Inflammation

• Published in: International journal of molecular sciences Vol. 21; no. 23; p. 9165
• Main Authors: Chulkina, Marina, Beswick, Ellen J, Pinchuk, Irina V
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-12-2020; MDPI
• Subjects: Abnormalities; Animals; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - genetics; B7-H1 Antigen - immunology; B7-H1 Antigen - metabolism; Biomarkers; Cancer; Cancer immunotherapy; Colon; Complex systems; Cytokines; Dendritic cells; Digestive system; Disease Progression; Disease Susceptibility; Fibrosis; Gastrointestinal Diseases - etiology; Gastrointestinal Diseases - metabolism; Gastrointestinal Diseases - pathology; gastrointestinal inflammation; Gastrointestinal tract; Homeostasis; Humans; Immune Checkpoint Inhibitors - pharmacology; Immune Checkpoint Inhibitors - therapeutic use; Immune Tolerance - genetics; Immunoglobulins; Immunoregulation; Immunotherapy; Inflammation; inflammatory bowel disease; Inflammatory Bowel Diseases - diagnosis; Inflammatory Bowel Diseases - etiology; Inflammatory Bowel Diseases - metabolism; Inflammatory Bowel Diseases - therapy; Inflammatory diseases; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Lymphocytes; Lymphocytes T; Microbiomes; Microbiota; Microorganisms; Molecular Targeted Therapy; Mucosa; Nutrients; Pathology; PD-1 protein; PD-L1; PD-L1 protein; Review; Rodents; Signal transduction; Small intestine; Stimulators; gastrointestinal inflammation; PD-L1; homeostasis; inflammatory bowel disease
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21239165

The gastrointestinal (GI) mucosa is among the most complex systems in the body. It has a diverse commensal microbiome challenged continuously by food and microbial components while delivering essential nutrients and defending against pathogens. For these reasons, regulatory cells and receptors are likely to play a central role in maintaining the gut mucosal homeostasis. Recent lessons from cancer immunotherapy point out the critical role of the B7 negative co-stimulator PD-L1 in mucosal homeostasis. In this review, we summarize the current knowledge supporting the critical role of PD-L1 in gastrointestinal mucosal tolerance and how abnormalities in its expression and signaling contribute to gut inflammation and cancers. Abnormal expression of PD-L1 and/or the PD-1/PD-L1 signaling pathways have been observed in the pathology of the GI tract. We also discuss the current gap in our knowledge with regards to PD-L1 signaling in the GI tract under homeostasis and pathology. Finally, we summarize the current understanding of how this pathway is currently targeted to develop novel therapeutic approaches.