Chronic Ethanol Feeding Induces Subset Loss and Hyporesponsiveness in Skin T Cells. (11th February 2014)

• Record Type: Journal Article
• Authors: Parlet, Corey P.; Waldschmidt, Thomas J.; Schlueter, Annette J.
• Is Part Of: Alcoholism. Volume 38:Number 5(2014:May)
• Page Start: 1356
• Page End: 1364
• Publication Date: 2014-02-11
• Subjects: Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.12358
• Languages: English
• ISSNs: 0145-6008

Abstract

<abstract abstract-type="main" id="acer12358-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="acer12358-sec-0001" sec-type="section"> <title>Background</title> <p>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.</p> </sec> <sec id="acer12358-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="acer12358-sec-0003" sec-type="section"> <title>Results</title> <p>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<sup>+</sup> regulatory T cells (Tregs) as well as CD3hi, Vγ3<sup>+</sup> and CD3int, Vγ3<sup>−</sup> 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.</p> </sec> <sec id="acer12358-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>