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T-cell regulation of neutrophil infiltrate at the early stages of a murine colitis model

Pieter PE van Lierop, Colin de Haar, Dicky J Lindenbergh-Kortleve, Ytje Simons-Oosterhuis, Leonie S van Rijt, Bart Lambrecht (UGent) , Johanna C Escher, Janneke N Samsom and Edward ES Nieuwenhuis
(2010) INFLAMMATORY BOWEL DISEASES. 16(3). p.442-451
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Abstract
Background: T-cells are a main target for antiinflammatory drugs in inflammatory bowel disease. As the innate immune system is also implicated in the pathogenesis of these diseases, T-cell suppressors may not only inhibit T-cell-dependent production of proinflammatory mediators but also affect innate immune cell function. Specifically, these drugs may impair innate immune cell recruitment and activation through inhibition of T-cells or act independent of T-cell modulation. We explored the extent of immune modulation by the T-cell inhibitor tacrolimus in a murine colitis model. Methods: We assessed the effects of tacrolimus on trinitro-benzene sulphonic acid (TNBS) colitis in wildtype and Rag2-deficient mice. The severity of colitis was assessed by means of histological scores and weight loss. We further characterized the inflammation using immunohistochemistry and by analysis of isolated intestinal leukocytes at various stages of disease. Results: Tacrolimus-treated wildtype mice were less sensitive to colitis and had fewer activated T-cells. Inhibition of T-cell function was associated with strongly diminished recruitment of infiltrating neutrophils in the colon at the early stages of this model. In agreement, immunohistochemistry demonstrated that tacrolimus inhibited production of the neutrophil chemoattractants CXCL I and CXCL2. Rag2-deficient mice displayed an enhanced baseline level of lamina propria neutrophils that was moderately increased in TNBS colitis and remained unaffected by tacrolimus. Conclusions: Both the innate and the adaptive mucosal immune system contribute to TNBS colitis. Tacrolimus suppresses colitis directly through inhibition of T-cell activation and by suppression of T-cell-mediated recruitment of neutrophils.
Keywords
CALCINEURIN INHIBITORS, ULCERATIVE-COLITIS, CROHNS-DISEASE, TNBS-INDUCED COLITIS, NITRIC-OXIDE SYNTHASE, INTESTINAL EPITHELIAL-CELLS, ORAL TACROLIMUS FK506, INFLAMMATORY-BOWEL-DISEASE, TNBS colitis, neutrophils, T-cell, innate immune system, DENDRITIC CELLS, DOWN-REGULATION

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MLA
van Lierop, Pieter PE, et al. “T-Cell Regulation of Neutrophil Infiltrate at the Early Stages of a Murine Colitis Model.” INFLAMMATORY BOWEL DISEASES, vol. 16, no. 3, 2010, pp. 442–51, doi:10.1002/ibd.21073.
APA
van Lierop, P. P., de Haar, C., Lindenbergh-Kortleve, D. J., Simons-Oosterhuis, Y., van Rijt, L. S., Lambrecht, B., … Nieuwenhuis, E. E. (2010). T-cell regulation of neutrophil infiltrate at the early stages of a murine colitis model. INFLAMMATORY BOWEL DISEASES, 16(3), 442–451. https://doi.org/10.1002/ibd.21073
Chicago author-date
Lierop, Pieter PE van, Colin de Haar, Dicky J Lindenbergh-Kortleve, Ytje Simons-Oosterhuis, Leonie S van Rijt, Bart Lambrecht, Johanna C Escher, Janneke N Samsom, and Edward ES Nieuwenhuis. 2010. “T-Cell Regulation of Neutrophil Infiltrate at the Early Stages of a Murine Colitis Model.” INFLAMMATORY BOWEL DISEASES 16 (3): 442–51. https://doi.org/10.1002/ibd.21073.
Chicago author-date (all authors)
van Lierop, Pieter PE, Colin de Haar, Dicky J Lindenbergh-Kortleve, Ytje Simons-Oosterhuis, Leonie S van Rijt, Bart Lambrecht, Johanna C Escher, Janneke N Samsom, and Edward ES Nieuwenhuis. 2010. “T-Cell Regulation of Neutrophil Infiltrate at the Early Stages of a Murine Colitis Model.” INFLAMMATORY BOWEL DISEASES 16 (3): 442–451. doi:10.1002/ibd.21073.
Vancouver
1.
van Lierop PP, de Haar C, Lindenbergh-Kortleve DJ, Simons-Oosterhuis Y, van Rijt LS, Lambrecht B, et al. T-cell regulation of neutrophil infiltrate at the early stages of a murine colitis model. INFLAMMATORY BOWEL DISEASES. 2010;16(3):442–51.
IEEE
[1]
P. P. van Lierop et al., “T-cell regulation of neutrophil infiltrate at the early stages of a murine colitis model,” INFLAMMATORY BOWEL DISEASES, vol. 16, no. 3, pp. 442–451, 2010.
@article{1081480,
  abstract     = {{Background: T-cells are a main target for antiinflammatory drugs in inflammatory bowel disease. As the innate immune system is also implicated in the pathogenesis of these diseases, T-cell suppressors may not only inhibit T-cell-dependent production of proinflammatory mediators but also affect innate immune cell function. Specifically, these drugs may impair innate immune cell recruitment and activation through inhibition of T-cells or act independent of T-cell modulation. We explored the extent of immune modulation by the T-cell inhibitor tacrolimus in a murine colitis model. 
Methods: We assessed the effects of tacrolimus on trinitro-benzene sulphonic acid (TNBS) colitis in wildtype and Rag2-deficient mice. The severity of colitis was assessed by means of histological scores and weight loss. We further characterized the inflammation using immunohistochemistry and by analysis of isolated intestinal leukocytes at various stages of disease.
Results: Tacrolimus-treated wildtype mice were less sensitive to colitis and had fewer activated T-cells. Inhibition of T-cell function was associated with strongly diminished recruitment of infiltrating neutrophils in the colon at the early stages of this model. In agreement, immunohistochemistry demonstrated that tacrolimus inhibited production of the neutrophil chemoattractants CXCL I and CXCL2. Rag2-deficient mice displayed an enhanced baseline level of lamina propria neutrophils that was moderately increased in TNBS colitis and remained unaffected by tacrolimus.
Conclusions: Both the innate and the adaptive mucosal immune system contribute to TNBS colitis. Tacrolimus suppresses colitis directly through inhibition of T-cell activation and by suppression of T-cell-mediated recruitment of neutrophils.}},
  author       = {{van Lierop, Pieter PE and de Haar, Colin and Lindenbergh-Kortleve, Dicky J and Simons-Oosterhuis, Ytje and van Rijt, Leonie S and Lambrecht, Bart and Escher, Johanna C and Samsom, Janneke N and Nieuwenhuis, Edward ES}},
  issn         = {{1078-0998}},
  journal      = {{INFLAMMATORY BOWEL DISEASES}},
  keywords     = {{CALCINEURIN INHIBITORS,ULCERATIVE-COLITIS,CROHNS-DISEASE,TNBS-INDUCED COLITIS,NITRIC-OXIDE SYNTHASE,INTESTINAL EPITHELIAL-CELLS,ORAL TACROLIMUS FK506,INFLAMMATORY-BOWEL-DISEASE,TNBS colitis,neutrophils,T-cell,innate immune system,DENDRITIC CELLS,DOWN-REGULATION}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{442--451}},
  title        = {{T-cell regulation of neutrophil infiltrate at the early stages of a murine colitis model}},
  url          = {{http://doi.org/10.1002/ibd.21073}},
  volume       = {{16}},
  year         = {{2010}},
}
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