title: Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis.
abstract: OBJECTIVE
  The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKT cells.
  
  
  METHODS
  We measured circulating and psoriatic plaque iNKT cell numbers in two patients with type 2 diabetes and psoriasis before and after commencing GLP-1 analogue therapy. In addition, we investigated the in vitro effects of GLP-1 on iNKT cells and looked for a functional GLP-1 receptor on these cells.
  
  
  RESULTS
  The Psoriasis Area and Severity Index improved in both patients following 6 weeks of GLP-1 analogue therapy. This was associated with an alteration in iNKT cell number, with an increased number in the circulation and a decreased number in psoriatic plaques. The GLP-1 receptor was expressed on iNKT cells, and GLP-1 induced a dose-dependent inhibition of iNKT cell cytokine secretion, but not cytolytic degranulation in vitro.
  
  
  CONCLUSIONS
  The clinical effect observed and the direct interaction between GLP-1 and the immune system raise the possibility of therapeutic applications for GLP-1 in inflammatory conditions such as psoriasis.
authors: Department of Endocrinology, St Vincent's University Hospital, University College Dublin, Dublin 4, Ireland.
authors: A E
authors: AE
authors: Hogan
authors: A M
authors: AM
authors: Tobin
authors: T
authors: T
authors: Ahern
authors: M A
authors: MA
authors: Corrigan
authors: G
authors: G
authors: Gaoatswe
authors: R
authors: R
authors: Jackson
authors: V
authors: V
authors: O'Reilly
authors: L
authors: L
authors: Lynch
authors: D G
authors: DG
authors: Doherty
authors: P N
authors: PN
authors: Moynagh
authors: B
authors: B
authors: Kirby
authors: J
authors: J
authors: O'Connell
authors: D
authors: D
authors: O'Shea
mesh_terms: D002452:Cell Count; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000819:agonists / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D007155:Immunologic Factors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009765:Obesity / Q000150:complications; D011565:Psoriasis / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018027:Receptors, Glucagon / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007155:Immunologic Factors; D012333:RNA, Messenger; D018027:Receptors, Glucagon; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1