Late Crohn's disease patients present an increase in peripheral Th17 cells and cytokine production compared with early patients.
BACKGROUND
Th1 and Th17 cells have been implicated in Crohn's disease (CD) pathophysiology and may play a role in disease persistence. Aim To determine Th1 and Th17 responses in intestine and peripheral blood of early (<32 weeks since initial symptoms) and late (>2 years) CD patients.


METHODS
Cytokine mRNA in intestinal biopsies was determined by RT-PCR. Cytokine concentration in culture was measured by ELISA and cytokine-producing cells were identified by intracellular staining.


RESULTS
The inflamed mucosa showed significantly increased IL-17 mRNA levels compared with non-inflamed areas, both in early and late CD patients. However, only patients with late (n = 12), but not early (n = 9), active disease showed increased IL-17 production, as well as a significantly higher percentage of IL-17(+)CD4(+) cells in blood, compared with controls (n = 12) or patients in remission (n = 13). Moreover, cultured peripheral CD4(+) cells from late active CD patients presented significantly higher percentages of IL-17(+), IL-22(+) and IFN-gamma(+) and a significantly increased production of IL-17 and IL-22, but not IFN-gamma(+).


CONCLUSIONS
Increased IL-17 gene transcription is common to early and late CD mucosa. However, exacerbated Th17 responses in the peripheral blood appear only in late disease. We propose that this population may constitute a mechanism of perpetuating the disease.
Veny
M
M
Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas, CIBER-EHD, Barcelona, Spain.
Esteller
M
M
Ricart
E
E
Piqué
J M
JM
Panés
J
J
Salas
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003424:Crohn Disease / Q000097:blood / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014158:Transcription, Genetic; D055815:Young Adult
D016207:Cytokines; D020381:Interleukin-17; D012333:RNA, Messenger