Higher constitutive IL15R alpha expression and lower IL-15 response threshold in coeliac disease patients.
The IL-15 triggering effect of gliadin is not exclusive to coeliac disease (CD) patients, whereas the secondary response is CD specific. We have studied the expression of the IL-15 receptor, and the IL-15 response upon stimulation, in non-CD and CD patients, and the possible existence of a lower immunological threshold in the latter. Forty-two CD patients (20 on a gluten-containing diet, GCD, and 22 on gluten-free diet, GFD) and 24 non-CD healthy individuals were studied. IL15R alpha mRNA expression, and tissue characterization, were assayed in the duodenum. Biopsies from six CD patients on GFD and 10 non-CD individuals were studied in vitro using organ culture in basal conditions, as well as after IL-15 stimulation discarding basal IL-15 production. Secretion of immune mediators was measured in the culture supernatants. IL15R alpha mRNA expression was increased in CD patients, as compared with non-CD controls (on GFD P = 0.0334, on GCD P = 0.0062, respectively), and confirmed also by immunofluorescence. No differences were found between CD patients on GFD and on GCD. After in vitro IL-15 stimulation, IL15R alpha expression was only triggered in non-CD controls (P = 0.0313), though it remained increased in CD patients. Moreover, IL-15 induced a more intense immunological response in CD patients after triggering the production of both nitrites and IFN gamma (P = 0.0313, P = 0.0313, respectively). Gliadin-induced IL15 has a lower response threshold in CD patients, leading to the production of other immune mediators and the development of the intestinal lesion, and thus magnifying its effects within the CD intestine.
Bernardo
D
D
Mucosal Immunology Laboratory, Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid-CSIC, Valladolid, Spain.
Garrote
J A
JA
Allegretti
Y
Y
León
A
A
Gómez
E
E
Bermejo-Martin
J F
JF
Calvo
C
C
Riestra
S
S
Fernández-Salazar
L
L
Blanco-Quirós
A
A
Chirdo
F
F
Arranz
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western / Q000379:methods; D016022:Case-Control Studies; D002446:Celiac Disease / Q000178:diet therapy / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004386:Duodenum / Q000276:immunology*; D005260:Female; D005983:Glutens / Q000276:immunology; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D053647:Receptors, Interleukin-15 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C508024:IL15RA protein, human; D019409:Interleukin-15; D012333:RNA, Messenger; D053647:Receptors, Interleukin-15; D005983:Glutens