title: Restraint stress and stress hormones significantly impact T lymphocyte migration and function through specific alterations of the actin cytoskeleton.
abstract: Stress triggers complex response mechanisms designed to recognize and adapt to perturbations in homeostasis. The immune system is highly responsive to stress, although the complete mechanisms linking stress and immune mediators including T lymphocytes, are not fully understood. Stress exerts its effects on immune effectors through two primary pathways: the sympathetic-adrenal-medullary pathway, and the hypothalamic-pituitary-adrenal pathway which modulate adaptive immunity and lymphocyte migration. In this report we show that stress via release of stress hormones induces early T cell activation and greatly impacts the cytoskeleton by modulating numerous actin-regulating proteins. In particular, proteomic profiling revealed significant decreases in numerous key actin-binding proteins including moesin. Although confocal microscopy showed that moesin and actin were uniformly distributed on the surface of resting T cells, a remarkable polarization and redistribution of moesin and actin was observed following treatment with stress hormones with moesin localizing at the distal pole complex. In addition, the alteration in moesin localization and eventual decrease in expression were accompanied by a loss of CD43; a receptor involved in negatively regulating T cell activation. In conclusion, we have defined a novel molecular mechanism whereby stress hormones negatively impact T cell activation and migration through regulation of key cytoskeletal and plasma membrane factors.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. flintms@upmc.edu
authors.forename: Melanie S
authors.initials: MS
authors.lastname: Flint
authors.forename: Raluca A
authors.initials: RA
authors.lastname: Budiu
authors.forename: Pang-ning
authors.initials: PN
authors.lastname: Teng
authors.forename: Mai
authors.initials: M
authors.lastname: Sun
authors.forename: Donna B
authors.initials: DB
authors.lastname: Stolz
authors.forename: Megan
authors.initials: M
authors.lastname: Lang
authors.forename: Brian L
authors.initials: BL
authors.lastname: Hood
authors.forename: Anda M
authors.initials: AM
authors.lastname: Vlad
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Conrads
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D002395:Catecholamines / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure*; D005260:Female; D005938:Glucocorticoids / Q000502:physiology; D015759:Ionomycin / Q000494:pharmacology; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics; D051917:Leukosialin / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics; D040901:Proteomics; D012149:Restraint, Physical / Q000009:adverse effects*; D013312:Stress, Physiological / Q000276:immunology* / Q000502:physiology; D013315:Stress, Psychological / Q000276:immunology* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000099192:CD69 Antigens
chemical_list: D000199:Actins; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002395:Catecholamines; D005938:Glucocorticoids; D015759:Ionomycin; D037181:Lectins, C-Type; D051917:Leukosialin; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D013755:Tetradecanoylphorbol Acetate; D000099192:CD69 Antigens; C497863:Spn protein, mouse; C071058:moesin