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Chronic Ethanol Feeding Induces Subset Loss and Hyporesponsiveness in Skin T Cells
Author(s) -
Parlet Corey P.,
Waldschmidt Thomas J.,
Schlueter Annette J.
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12358
Subject(s) - ionomycin , foxp3 , immunology , t cell , immune system , cytokine , stimulation , population , ex vivo , flow cytometry , biology , endocrinology , medicine , in vivo , environmental health , microbiology and biotechnology
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 (Et OH ) 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 Et OH in the drinking water for 12 to 16 weeks. Flow cytometry was used to evaluate impact of Et OH 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 Et OH 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 Et OH 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 CD 3hi, Vγ3 + and CD 3int, Vγ3 − dermal γδ T cells. Et OH ‐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‐ CD 3 stimulation. Additionally, the capacity of lymph node γδ T cells to produce IL ‐17 following anti‐ CD 3 and PMA /ionomycin stimulation was impaired by chronic Et OH feeding. Conclusions Chronic Et OH feeding induced defects in both numbers and function of multiple skin T cell subsets. The decreased density and poor responsiveness of DETC s 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 Et OH and provide new mechanisms to help explain the propensity of alcoholics to suffer skin infection.