Regulatory T Cells Restrict Permeability to Bacterial Antigen Translocation and Preserve Short-Chain Fatty Acids in Experimental Cirrhosis.
Oriol JuanolaPaula PiñeroIsabel Gómez-HurtadoEsther CaparrósRocío García-VillalbaAlicia MarínPedro ZapaterFabián TarínJosé M González-NavajasFrancisco A Tomás-BarberánRubén FrancésPublished in: Hepatology communications (2018)
Intestinal permeability to translocation of bacterial products is increased in cirrhosis. Regulatory T cells (Tregs) remain central to the interplay between the host and microbial milieu. We propose that Tregs are involved in promoting gut barrier integrity and a balanced interaction with gut microbiota-derived short-chain fatty acids (SCFAs). Carbon tetrachloride cirrhosis was induced in wild-type and recombination activating gene 1 (Rag1)-/- mice. Naive T cells and Treg cells were transferred into Rag1 -/- mice. Intestinal permeability was assessed in vivo after lipopolysaccharide (LPS) oral administration, and bacterial DNA presence was evaluated in mesenteric lymph nodes. Transcript and protein levels of tight-junction (TJ) proteins were measured in colonic tissue. Intestinal T helper profile in response to Escherichia coli (E. coli) was determined by flow cytometry. SCFAs were measured by gas chromatography-mass spectrometry in colonic content before and after E. coli challenge. Rag1 -/- mice showed significantly increased permeability to LPS and bacterial DNA translocation rate compared with control mice. Naive T and Treg cotransfer significantly reduced gut permeability to bacterial antigen translocation and restored TJ protein expression in Rag1 -/- mice. Naive T and Treg replenishment in Rag1 -/- mice restrained proinflammatory differentiation of intestinal lymphocytes in response to E. coli. The main SCFA concentration resulted in significant reduction in Rag1 -/- mice after E. coli administration but remained unaltered after naive T and Tregs cotransfer. The reduced expression of SCFA receptors induced by E. coli was reestablished following naive T and Treg reconstitution in Rag1 -/- mice. Conclusion: The restriction of gut permeability, local inflammatory differentiation, and loss of bacteria-derived SCFAs foster the value of Tregs in preventing bacterial translocation in cirrhosis.
Keyphrases
- escherichia coli
- regulatory t cells
- high fat diet induced
- wild type
- lymph node
- fatty acid
- endothelial cells
- hiv infected
- inflammatory response
- dendritic cells
- type diabetes
- induced apoptosis
- toll like receptor
- early stage
- cell death
- mass spectrometry
- gene expression
- signaling pathway
- blood brain barrier
- ulcerative colitis
- single molecule
- rna seq
- liver injury
- antiretroviral therapy
- transcription factor
- endoplasmic reticulum stress
- drug induced
- high resolution
- metabolic syndrome
- protein protein
- dna methylation
- sentinel lymph node