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Skin cells, but not T cells, are resistant to indoleamine 2, 3‐dioxygenase (IDO) expressed by allogeneic fibroblasts
Author(s) -
Forouzandeh Farshad,
Jalili Reza B.,
Germain Marc,
Duronio Vincent,
Ghahary Aziz
Publication year - 2008
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2008.00377.x
Subject(s) - indoleamine 2,3 dioxygenase , immune system , apoptosis , human skin , microbiology and biotechnology , biology , cancer research , epidermis (zoology) , immune tolerance , chemistry , immunology , tryptophan , biochemistry , genetics , amino acid , anatomy
We have previously demonstrated that indoleamine 2, 3‐dioxygenase (IDO) expressed by dermal fibroblasts generated a tryptophan deficient environment in which immune cells, but not skin cells, undergo apoptosis. However, the mechanism by which primary skin cells such as fibroblasts and keratinocytes are resistant to this culture environment is not elucidated. Here, we asked the question of whether the activity of the general control nonderepressing‐2 (GCN2) kinase pathway in primary immune and skin cells is differently regulated in response to IDO‐induced tryptophan deficient environment. Before addressing this question, the expression of IDO in IDO‐adenoviral infected fibroblasts, as a source of IDO expression, was validated. We then demonstrated a significant immunosuppressive effect of IDO expression in primary human T cells co‐cultured with IDO expressing fibroblasts in the presence of allogeneic pieces of either epidermis or full thickness skin. Evaluating the mechanism by which skin cells, but not T cells, are resistant to IDO induced low tryptophan environment, we then co‐cultured IDO‐expressing fibroblasts with bystander human T cells, the fibroblasts, or keratinocytes for 3 days. The results showed a significant activation of apoptotic pathway as analyzed by caspase‐3 induction as well as the expression of CHOP, a downstream effector of GCN2 kinase pathway in T cells, but not in skin cells.