Interleukin-23 and T helper 17-type responses in intestinal inflammation: from cytokines to T-cell plasticity

TY - JOUR

T1 - Interleukin-23 and T helper 17-type responses in intestinal inflammation: from cytokines to T-cell plasticity

AU - Morrison, Peter J.

AU - Ballantyne, Sarah J.

AU - Kullberg, Marika C.

PY - 2011/8

Y1 - 2011/8

N2 - Interleukin-23 (IL-23) plays an essential role in driving intestinal pathology in experimental models of both T-cell-dependent and innate colitis. Furthermore, genome-wide association studies have identified several single-nucleotide polymorphisms in the IL-23 receptor (IL-23R) gene that are associated with either susceptibility or resistance to inflammatory bowel disease in humans. Although initially found to support the expansion and maintenance of CD4(+) T helper 17 (Th17) cells, IL-23 is now recognized as having multiple effects on the immune response, including restraining Foxp3(+) regulatory T-cell activity and inducing the expression of Th17-type cytokines from non-T-cell sources. Here we focus on Th17 cells and their associated cytokines IL-17A, IL-17F, IL-21 and IL-22. We review studies performed in mouse models of colitis where these effector cytokines have been shown to have either a pathogenic or a tissue-protective function. We also discuss the heterogeneity found within the Th17 population and the phenomenon of plasticity of Th17 cells, in particular the ability of these lymphocytes to extinguish IL-17 expression and turn on interferon-gamma production to become Th1-like 'ex-Th17' cells. Interleukin-23 has been identified as a key driver in this process, and this may be an additional mechanism by which IL-23 promotes pathology in the intestinal tract. These 'ex-Th17' cells may contribute to disease pathogenesis through their secretion of pro-inflammatory mediators.

AB - Interleukin-23 (IL-23) plays an essential role in driving intestinal pathology in experimental models of both T-cell-dependent and innate colitis. Furthermore, genome-wide association studies have identified several single-nucleotide polymorphisms in the IL-23 receptor (IL-23R) gene that are associated with either susceptibility or resistance to inflammatory bowel disease in humans. Although initially found to support the expansion and maintenance of CD4(+) T helper 17 (Th17) cells, IL-23 is now recognized as having multiple effects on the immune response, including restraining Foxp3(+) regulatory T-cell activity and inducing the expression of Th17-type cytokines from non-T-cell sources. Here we focus on Th17 cells and their associated cytokines IL-17A, IL-17F, IL-21 and IL-22. We review studies performed in mouse models of colitis where these effector cytokines have been shown to have either a pathogenic or a tissue-protective function. We also discuss the heterogeneity found within the Th17 population and the phenomenon of plasticity of Th17 cells, in particular the ability of these lymphocytes to extinguish IL-17 expression and turn on interferon-gamma production to become Th1-like 'ex-Th17' cells. Interleukin-23 has been identified as a key driver in this process, and this may be an additional mechanism by which IL-23 promotes pathology in the intestinal tract. These 'ex-Th17' cells may contribute to disease pathogenesis through their secretion of pro-inflammatory mediators.

KW - colitis

KW - inflammation

KW - interferon-gamma

KW - interleukin-17A

KW - interleukin-23

KW - T helper 17 cells

KW - ROR-GAMMA-T

KW - GENOME-WIDE ASSOCIATION

KW - INNATE LYMPHOID-CELLS

KW - ACTIVE CROHNS-DISEASE

KW - NATURAL-KILLER-CELLS

KW - GROWTH-FACTOR-BETA

KW - INDUCER-LIKE CELLS

KW - HUMAN TH17 CELLS

KW - BOWEL-DISEASE

KW - CUTTING EDGE

UR - http://www.scopus.com/inward/record.url?scp=79959875101&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2567.2011.03454.x

DO - 10.1111/j.1365-2567.2011.03454.x

M3 - Literature review

SN - 0019-2805

VL - 133

SP - 397

EP - 408

JO - Immunology

JF - Immunology

IS - 4

ER -