MAIT cell activation in adolescents is impacted by bile acid concentrations and body weight.
A MendlerA PierzchalskiMario BauerS RöderA SattlerM StandlM BorteM von BergenU Rolle-KampczykGunda HerberthPublished in: Clinical and experimental immunology (2020)
Bile acids (BAs) are produced by liver hepatocytes and were recently shown to exert functions additional to their well-known role in lipid digestion. As yet it is not known whether the mucosal-associated invariant T (MAIT) cells, which represent 10-15% of the hepatic T cell population, are affected by BAs. The focus of the present investigation was on the association of BA serum concentration with MAIT cell function and inflammatory parameters as well as on the relationship of these parameters to body weight. Blood samples from 41 normal weight and 41 overweight children of the Lifestyle Immune System Allergy (LISA) study were analyzed with respect to MAIT cell surface and activation markers [CD107a, CD137, CD69, interferon (IFN)-γ, tumor necrosis factor (TNF)-α] after Escherichia coli stimulation, mRNA expression of promyelocytic leukemia zinc finger protein (PLZF) and major histocompatibility complex class I-related gene protein (MR1), the inflammatory markers C-reactive protein (CRP), interleukin (IL)-8 and macrophage inflammatory protein (MIP)-1α as well as the concentrations of 13 conjugated and unconjugated BAs. Higher body weight was associated with reduced MAIT cell activation and expression of natural killer cell marker (NKp80) and chemokine receptor (CXCR3). BA concentrations were positively associated with the inflammatory parameters CRP, IL-8 and MIP-1α, but were negatively associated with the number of activated MAIT cells and the MAIT cell transcription factor PLZF. These relationships were exclusively found with conjugated BAs. BA-mediated inhibition of MAIT cell activation was confirmed in vitro. Thus, conjugated BAs have the capacity to modulate the balance between pro- and anti-inflammatory immune responses.
Keyphrases
- body weight
- single cell
- immune response
- cell therapy
- escherichia coli
- transcription factor
- physical activity
- induced apoptosis
- oxidative stress
- rheumatoid arthritis
- young adults
- binding protein
- anti inflammatory
- photodynamic therapy
- type diabetes
- dendritic cells
- body mass index
- cardiovascular disease
- acute myeloid leukemia
- stem cells
- cell proliferation
- computed tomography
- magnetic resonance imaging
- cell cycle arrest
- poor prognosis
- gene expression
- bone marrow
- small molecule
- toll like receptor
- mesenchymal stem cells
- signaling pathway
- inflammatory response
- amino acid
- copy number
- protein protein
- genome wide identification
- contrast enhanced
- infectious diseases