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  4. Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease
Traditionally, Crohn's disease has been associated with a Th1
cytokine profile, while Th2 cytokines are modulators of ulcerative
colitis. This concept has been challenged by the description of
tolerising regulatory T cells (Treg) and by proinflammatory Th17
cells, a novel T cell population characterised by the master
transcription factor ROR\textgreekgt, the surface markers IL23R and
CCR6, and by production of the proinflammatory cytokines IL17A,
IL17F, IL21, IL22 and IL26, and the chemokine CCL20. Th17 cells
differentiate under the influence of IL1\textgreekb, IL6, IL21 and
IL23. Recent studies indicate that TGF\textgreekb is essential not
only for the development of murine Th17 cells but also for
differentiation of human Th17 cells. TGF\textgreekb reciprocally
regulates the differentiation of inflammatory Th17 cells and
suppressive Treg subsets, with the concomitant presence of
proinflammatory cytokines favouring Th17 cell differentiation.
Several studies demonstrated an important role of Th17 cells in
intestinal inflammation, particularly in Crohn's disease.
Genome-wide association studies indicate that IL23R and five
additional genes involved in Th17 differentiation (IL12B, JAK2,
STAT3, CCR6 and TNFSF15) are associated with susceptibility to
Crohn's disease and partly also to ulcerative colitis. Taken
together, both Th1 and Th17 cells are important mediators of
inflammation in Crohn's disease, although activities previously
ascribed to IL12 may be mediated by IL23. Anti-IL12/IL23p40
antibody therapy, which targets both Th1 and Th17 cells, is
effective in Crohn's disease. However, the complex relationship
between Th1 and Th17 cells has not been completely analysed. This
will be of great importance to delineate the specific contributions
of these cells to Crohn's disease and other autoimmune diseases.

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„Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease“

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