Heat shock protein-derived T-cell epitopes contribute to autoimmune inflammation in pediatric Crohn's disease.
Pediatric Crohn's disease is a chronic auto inflammatory bowel disorder affecting children under the age of 17 years. A putative etiopathogenesis of Crohn's disease (CD) is associated with disregulation of immune response to antigens commonly present in the gut microenvironment. Heat shock proteins (HSP) have been identified as ubiquitous antigens with the ability to modulate inflammatory responses associated with several autoimmune diseases. The present study tested the contribution of immune responses to HSP in the amplification of autoimmune inflammation in chronically inflamed mucosa of pediatric CD patients. Colonic biopsies obtained from normal and CD mucosa were stimulated with pairs of Pan HLA-DR binder HSP60-derived peptides (human/bacterial homologues). The modulation of RNA and protein levels of induced proinflammatory cytokines were measured. We identified two epitopes capable of sustaining proinflammatory responses, specifically TNF< and IFN induction, in the inflamed intestinal mucosa in CD patients. The responses correlated positively with clinical and histological measurements of disease activity, thus suggesting a contribution of immune responses to HSP in pediatric CD site-specific mucosal inflammation.
Puga Yung
Gisella L
GL
Department of Medicine/Pediatrics, University of California San Diego, La Jolla, California, United States of America.
Fidler
Meredith
M
Albani
Erika
E
Spermon
Naomi
N
Teklenburg
Gijs
G
Newbury
Robert
R
Schechter
Nicole
N
van den Broek
Theo
T
Prakken
Berent
B
Billetta
Rosario
R
Dohil
Ranjan
R
Albani
Salvatore
S
D000293:Adolescent; D015551:Autoimmunity; D018834:Chaperonin 60 / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry*; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D008297:Male; D010641:Phenotype
D018834:Chaperonin 60; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006360:Heat-Shock Proteins