Colitis Promotes a Pathological Condition of the Liver in the Absence of Foxp3+ Regulatory T Cells.
Franziska MathiesNiklas SteffensDoerte KleinschmidtFriederike StuhlmannFrancis J HuberUrmi RoyThomas MeyerMarc LuetgehetmannMareike von PetersdorffOliver SeizJohannes HerkelChristoph SchrammRichard A FlavellNicola GaglianiChristian F KrebsUlf PanzerZeinab AbdullahTill StrowigTanja BedkeSamuel HuberPublished in: Journal of immunology (Baltimore, Md. : 1950) (2018)
Inflammatory bowel disease is associated with extraintestinal diseases such as primary sclerosing cholangitis in the liver. Interestingly, it is known that an imbalance between Foxp3+ regulatory T cells (Treg) and Th17 cells is involved in inflammatory bowel disease and also in primary sclerosing cholangitis. To explain these associations, one hypothesis is that intestinal inflammation and barrier defects promote liver disease because of the influx of bacteria and inflammatory cells to the liver. However, whether and how this is linked to the Treg and Th17 cell imbalance is unclear. To address this, we used dextran sodium sulfate (DSS) and T cell transfer colitis mouse models. We analyzed the pathological conditions of the intestine and liver on histological, cellular, and molecular levels. We observed bacterial translocation and an influx of inflammatory cells, in particular Th17 cells, to the liver during colitis. In the DSS colitis model, in which Treg were concomitantly increased in the liver, we did not observe an overt pathological condition of the liver. In contrast, the T cell-mediated colitis model, in which Treg are not abundant, was associated with marked liver inflammation and a pathological condition. Of note, upon depletion of Treg in DEREG mice, DSS colitis promotes accumulation of Th17 cells and a pathological condition of the liver. Finally, we studied immune cell migration using KAEDE mice and found that some of these cells had migrated directly from the inflamed intestine into the liver. Overall, these data indicate that colitis can promote a pathological condition of the liver and highlight an important role of Treg in controlling colitis-associated liver inflammation.
Keyphrases
- regulatory t cells
- induced apoptosis
- oxidative stress
- cell cycle arrest
- ulcerative colitis
- dendritic cells
- magnetic resonance
- immune response
- endoplasmic reticulum stress
- mouse model
- metabolic syndrome
- adipose tissue
- cell proliferation
- insulin resistance
- deep learning
- big data
- pi k akt
- single molecule
- high fat diet induced