Ethanol consumption inhibits TFH cell responses and the development of autoimmune arthritis.
Vugar AzizovKatharina DietelFranziska SteffenKerstin DürholzJulia MeidenbauerSébastien LucasMichael FrechYasunori OmataNarges TajikLisa KnipferAnne KolenbranderSilvia SeubertDennis LapuenteMaria V SokolovaJörg HofmannMatthias TenbuschAndreas RammingUlrike SteffenFalk NimmerjahnRalf LinkerStefan WirtzMartin HerrmannVladimir TemchuraKerstin SarterGeorg SchettMario M ZaissPublished in: Nature communications (2020)
Alcohol consumption is a consistent protective factor for the development of autoimmune diseases such as rheumatoid arthritis (RA). The underlying mechanism for this tolerance-inducing effect of alcohol, however, is unknown. Here we show that alcohol and its metabolite acetate alter the functional state of T follicular helper (TFH) cells in vitro and in vivo, thereby exerting immune regulatory and tolerance-inducing properties. Alcohol-exposed mice have reduced Bcl6 and PD-1 expression as well as IL-21 production by TFH cells, preventing proper spatial organization of TFH cells to form TFH:B cell conjugates in germinal centers. This effect is associated with impaired autoantibody formation, and mitigates experimental autoimmune arthritis. By contrast, T cell independent immune responses and passive models of arthritis are not affected by alcohol exposure. These data clarify the immune regulatory and tolerance-inducing effect of alcohol consumption.
Keyphrases
- alcohol consumption
- rheumatoid arthritis
- induced apoptosis
- cell cycle arrest
- immune response
- multiple sclerosis
- magnetic resonance imaging
- poor prognosis
- type diabetes
- magnetic resonance
- stem cells
- disease activity
- cell death
- metabolic syndrome
- signaling pathway
- bone marrow
- dendritic cells
- single cell
- regulatory t cells
- electronic health record
- drug delivery
- cell therapy
- machine learning
- binding protein
- long non coding rna
- inflammatory response
- artificial intelligence
- mesenchymal stem cells
- cancer therapy