Artikel
Acetylcholine modulates mucosal immune cells in Hirschsprung’s disease
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Veröffentlicht: | 21. April 2016 |
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Background: Hirschsprung’s disease (HD) is diagnosed shortly after birth and is characterized by the lack of enteric ganglions. Either before or after surgical correction some patients suffer from life-threatening HD associated enterocolitis, often due to opportunistic pathogen overgrowth. The lack of regulating enteric nervous cells leads to a hyper-innervation of the distal colon region by parasympathetic nerve fibers, secreting acetylcholine. Acetylcholine dampens inflammatory immune responses and is supposed to favor the generation of regulatory T cells. Regulatory T cells normaly maintain tolerance towards harmless pathogens whereas an accumulation of these cells could lead to an immunesuppressed state promoting opportunistic pathogen overgrowth. Understanding the implementation of regulatory T cells in the onset of enterocolitis will open new possibilities for therapeutical treatment.
Materials and methods: Colonic lymphocytes were isolated from different colonic segments of HD and control patients and the composition as well as phenotype of CD4 T cell subsets were assessed by flow cytometry (FACS). The expression level of acetylcholinesterase in different colon segments was determined by quantitative RT-PCR.
Results: Regulatory T cells accumulate in acetylcholine rich aganlionic colon segments of HD patients. Regulatory T cells exclusively increase in the musculature and are positive for the proliferation marker KI-67.
Conclusion: Our preliminary data show that regulatory T cells proliferate in the musculature of acetylcholine rich colon segments and could be involved in the onset of HD-associated enterocolitis by favoring the outgrowth of opportunistic pathogens.