Chronic Ethanol Feeding Induces Subset Loss and Hyporesponsiveness in Skin T Cells. (11th February 2014) - Parlet, Corey P.
Abstract Background Chronic alcoholism is associated with increased incidence and severity of cutaneous infection. Skin‐resident T cells orchestrate numerous immunological functions that are critically involved in both tissue homeostasis and cutaneous immunity. The impact of chronic ethanol (EtOH) exposure on skin T cells has not previously been examined; given their important role in maintaining the immune barrier function of the skin further study is warranted. Methods Mice were administered EtOH in the drinking water for 12 to 16 weeks. Flow cytometry was used to evaluate impact of EtOH feeding on skin T cell numbers, rates of proliferation, and apoptosis as well as activation marker expression and cytokine production after ex vivo stimulation. Results Chronic EtOH feeding caused a baseline reduction in dendritic epidermal T cell (DETC) numbers that corresponded with reduced expression of the activation marker JAML following phorbol 12‐myristate 13‐acetate (PMA)/ionomycin stimulation. Chronic EtOH feeding did not alter total numbers of dermal T cells, but specific subset loss was observed in Foxp3+ regulatory T cells (Tregs) as well as CD3hi, Vγ3+ and CD3int, Vγ3− dermal γδ T cells. EtOH‐induced dysfunction in the latter population, which represents prototypical interleukin‐17 (IL‐17)‐producing dermal γδT17s, was made evident by diminished IL‐17 production following anti‐CD3 stimulation. Additionally, the capacity of lymph node γδ T cells to produce IL‐17 following anti‐CD3 and PMA/ionomycin stimulation was impaired by chronic EtOH feeding. Conclusions Chronic EtOH feeding induced defects in both numbers and function of multiple skin T cell subsets. The decreased density and poor responsiveness of DETCs and γδT17 cells in particular would be expected to compromise immune effector mechanisms necessary to maintain a protective barrier and restrict pathogen invasion. These findings demonstrate the sensitivity of skin T cells to EtOH and provide new mechanisms to help explain the propensity of alcoholics to suffer skin infection.