Zusammenfassung
Recent studies indicate that chronic psychosocial stress favors the development of generalized immune dysfunction. During stressor exposure neuroendocrine factors affect numbers and functionality of leukocytes. However, the exact mechanisms leading to systemic changes in immune functions during stress are still not clear. During chronic subordinate colony housing, a model of chronic psychosocial ...
Zusammenfassung
Recent studies indicate that chronic psychosocial stress favors the development of generalized immune dysfunction. During stressor exposure neuroendocrine factors affect numbers and functionality of leukocytes. However, the exact mechanisms leading to systemic changes in immune functions during stress are still not clear. During chronic subordinate colony housing, a model of chronic psychosocial stress, mice developed spontaneous colonic inflammation. Decreased glucocorticoid signaling, induced by a combination of adrenal insufficiency and glucocorticoid resistance, was thought to prevent tempering of local immune cells, and to promote tissue inflammation. In this study we investigated changes in the systemic immune status after chronic subordinate colony housing and analyzed potential mechanisms underlying those alterations. Analysis of T helper cell subsets in peripheral lymph nodes revealed a reduction of regulatory T cells, accompanied by increased T cell effector functions. Generalized activation of T cells was shown by elevated cytokine production upon stimulation. In addition, we observed no apparent shift towards T helper type 2 responses. It is likely, that the previously reported hypocorticism in this stress model led to a steady production of inflammatory Th1, Th2, and Th17 cytokines and obstructed the shift towards an anti-inflammatory response. In conclusion, we established chronic subordinate colony housing as a model to investigate the outcome of stress on the systemic immune status. We also provide evidence that distinct T helper cell subtypes react differentially to the suppressive effect of glucocorticoids. (C) 2010 Elsevier Inc. All rights reserved.
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