title: T-Helper Cell-Mediated Islet Inflammation Contributes to β-Cell Dysfunction in Chronic Pancreatitis.
abstract: OBJECTIVE
  Beta-cell dysfunction and endocrine insufficiency in chronic pancreatitis (CP) is considered as a late manifestation emanating from fibrosis. To ascertain the role of T-helper cells in β-cell dysfunction, we enumerated circulating T-cell subsets, examined their infiltration into pancreatic islets, and assessed islet functions.
  
  
  METHODS
  Pancreatic tissues and peripheral blood were obtained from CP patients with/without diabetes. T cells were enumerated on flow cytometry and by immunostaining. Islets were assessed for glucose-stimulated insulin release (GSIR) and apoptosis (Annexin V/caspase-3). Islet proteins were probed for insulin gene transcription factor.
  
  
  RESULTS
  Circulating T-helper type 1 (Th1) cells were higher (P < 0.003) in CP patients with diabetes in comparison with control and CP patients without diabetes. Intra-islet colocalization of Th1 and Th17 cells was evident. In comparison with the controls, 2% ± 0.87% β cells from CP patients without diabetes were apoptotic whereas GSIR was decreased by 60% ± 12%, and 40% ± 9% from CP patients with diabetes were apoptotic, with minimal GSIR (1.42% ± 0.9%) in the remaining 60% viable cells. Western blots of islet proteins revealed an increase in STAT1 (signal transducer and activator of transcription 1) and a decrease in phosphorylated pancreatic duodenal homeobox (Pdx-1).
  
  
  CONCLUSIONS
  T cell-mediated inflammation is associated with β-cell dysfunction during progression of CP.
authors.affiliation: From the *Asian Healthcare Foundation and †Asian Institute of Gastroenterology, Somajiguda, Hyderabad, India.
authors.forename: Rupjyoti
authors.initials: R
authors.lastname: Talukdar
authors.forename: Mitnala
authors.initials: M
authors.lastname: Sasikala
authors.forename: Pondugala
authors.initials: P
authors.lastname: Pavan Kumar
authors.forename: Guduru Venkata
authors.initials: GV
authors.lastname: Rao
authors.forename: Rebala
authors.initials: R
authors.lastname: Pradeep
authors.forename: Duvvuru Nageshwar
authors.initials: DN
authors.lastname: Reddy
mesh_terms: D000328:Adult; D017209:Apoptosis; D015153:Blotting, Western; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D050500:Pancreatitis, Chronic / Q000097:blood / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; D007328:Insulin; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D005947:Glucose