The overall goal of these studies is to elucidate the mechanisms mediating the recent finding that under certain conditions stress can enhance skin immunity. We initially reported that acute of short-duration stress induces a redistribution of immune cells from the blood to organs such as the skin. Since the skin is the body's first line of defense, we examined the functional consequences of this leukocyte trafficking using the delayed type hypersensitivity (DTH) response as an in vivo assay for skin cell mediated immunity. Studies showed that acute stress experienced immediately before primary ( sensitization phase) or secondary (challenge phase) antigen exposure significantly enhanced skin DTH. In contrast, chronic stress suppressed skin DTH. In agreement with these studies, several investigators have reported stress-induced enhancement of DTH to different antigens administered to different sites of sensitization and challenge. The long- term objective of our research program is to elucidate the neuroendocrine and immune mediators and health consequences of the bi-directional effects of acute versus chronic stress on immune function. The overall goal of the proposed studies is to elucidate the mechanisms mediating the effects of acute stress on leukocyte trafficking and skin immunity. These studies will use wild type and gene knockout mice, immunoneutralization, flow cytometry, immunohistochemistry, in situ hybridization, RT-PCR, and ELISA to conduct analyses at the level of the organism, cell, protein, and gene expression.
Three specific aims will be addressed: 1)Identify cell adhesion molecules that mediate the stress-induced redistribution of leukocytes. 2) Identify leukocyte subpopulations that mediate a stress-induced enhancement of the sensitization and challenge phases of DTH. 3) Identify chemokines and cytokines that mediate a stress-induced enhancement of both phases of DTH. These studies are important because stress is suspected to play a role in the etiology of many diseases and we propose to study the effects of stress on two important immune parameters: Leukocyte trafficking, which is crucial for the surveillance and effector functions of the immune system. And DTH, which mediates aspects of immunoprotection (e.g. resistance to infections and cancer and post-vaccination immunity) and immunopathology (e.g. autoimmune, dermatitis, and granulomatous disorders). It is hoped that the elucidation of mechanisms such as those proposed here will facilitate the development of biomedical treatments designed to harness and individual's physiology to selectively enhance (during surgery, wound healing, infections, or cancer) or suppress (during autoimmune or inflammatory disorders) an immune response depending on the clinical needs to the patient.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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Special Emphasis Panel (ZRG1-IFCN-4 (06))
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Minnicozzi, Michael
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Ohio State University
Schools of Dentistry
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Dhabhar, Firdaus S (2018) The short-term stress response - Mother nature's mechanism for enhancing protection and performance under conditions of threat, challenge, and opportunity. Front Neuroendocrinol 49:175-192
Dhabhar, Firdaus S (2014) Effects of stress on immune function: the good, the bad, and the beautiful. Immunol Res 58:193-210
Dhabhar, Firdaus S (2013) Psychological stress and immunoprotection versus immunopathology in the skin. Clin Dermatol 31:18-30
Dhabhar, Firdaus S; Malarkey, William B; Neri, Eric et al. (2012) Stress-induced redistribution of immune cells--from barracks to boulevards to battlefields: a tale of three hormones--Curt Richter Award winner. Psychoneuroendocrinology 37:1345-68
Saul, Alison N; Oberyszyn, Tatiana M; Daugherty, Christine et al. (2005) Chronic stress and susceptibility to skin cancer. J Natl Cancer Inst 97:1760-7
Viswanathan, Kavitha; Dhabhar, Firdaus S (2005) Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation. Proc Natl Acad Sci U S A 102:5808-13
Viswanathan, Kavitha; Daugherty, Christine; Dhabhar, Firdaus S (2005) Stress as an endogenous adjuvant: augmentation of the immunization phase of cell-mediated immunity. Int Immunol 17:1059-69
Tseng, Raymond J; Padgett, David A; Dhabhar, Firdaus S et al. (2005) Stress-induced modulation of NK activity during influenza viral infection: role of glucocorticoids and opioids. Brain Behav Immun 19:153-64
Dhabhar, Firdaus S; Viswanathan, Kavitha (2005) Short-term stress experienced at time of immunization induces a long-lasting increase in immunologic memory. Am J Physiol Regul Integr Comp Physiol 289:R738-44
Gatien, Michelle L; Hotchkiss, Andrew K; Neigh, Gretchen N et al. (2004) Immune and stress responses in C57BL/6 and C3H/HeN mouse strains following photoperiod manipulation. Neuro Endocrinol Lett 25:267-72

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