Stress-Induced Neurogenic Inflammation in Murine Skin Skews Dendritic Cells Towards Maturation and Migration

Abstract

The skin continuously serves as a biosensor of multiple exogenous stressors and integrates the resulting responses with an individual's central and peripheral endogenous response systems to perceived stress; it also acts to protect against external challenges such as wounding and infection. We have previously shown in mice that stress induces nerve growth factor-and substance P-dependent neurogenic inflammation, which includes the prominent clustering of MHC class II ؉ cells. Because the contribution of dendritic cells (DCs) in response to stress is not well understood, we examined the role of DCs in neurogenic inflammation in murine skin using a well-established murine stress model. We show that sound stress increases the number of intradermal langerin Mammalian skin serves as a complex biological interface system that protects against external challenges such as wounding, infection, or UV radiation and even safeguards against viral and carcinogen-induced transformation. These complex functions only can be executed because skin represents far more than a simple mechanical barrier. It also constitutes a critical first barrier of immune defenses targeted against external stressors that crucially directs the linkage of innate and adaptive immunity. 1 Superimposed on this is the impact of psychological stress, which may challenge these complex interface functions of the skin.2 In this context, we previously introduced the existence of the brain-skin connection 3 by revealing that the skin and its appendages are not only vulnerable to key stress mediators such as Corticotropinreleasing hormone, substance P (SP), and nerve growth factor, but also are themselves potent sources of these stress response mediators. 4 -6 This-insufficiently defined-brain-skin connection provides the rationale for common skin responses to stress such as excessive Supported by the German Research Foundation (Deutsche Forschungsgemeinschaft; grants Ar 232/14-2 and Pa 345/11-2) and the Charité (UFF 99-648 and habilitation programs to R.A.J. and S.M.B.).

The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D)

“…230 And although chronic stress is best known to suppress immune function, 231 the types of acute and/or psychosocial stressors most likely to be associated with immediate risk of wounding and hence infection activate both innate and adaptive immunity. 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242 And while suppressing certain measures of adaptive immunity, chronic stress (whether experienced during childhood or as an adult) has been repeatedly associated with increased peripheral inflammatory biomarkers. 233, 243, 244, 245, 246, 247, 248 …”

Amyloid in skin and brain: What′s the link?

“…As it is known that inflammatory diseases may lead to amyloid formation in skin (82,104) and that stress may lead to skin inflammation (64–68,70–74), the connection of skin and brain in terms of inflammatory processes becomes evident. We speculate that neurogenic inflammation may contribute to amyloid formation in skin and that brain and skin are closely connected via amyloid deposits in AD.…”

“…Some important players have already been identified, such as corticotropin‐releasing hormone (CRH), nerve growth factor (NGF), neurotensin, substance P and various other neuropeptides (Fig. 1) (63,64,66–68,70–73). The hair follicle, for example, is both target for and source of immunomodulatory stress mediators, similar to the hypothalamus–pituitary–adrenal axis (66,68,74).…”

Stress-Related Programming of Autonomic Imbalance: Role in Allergy and Asthma

“…dendritic cells, epithelial cells (ECs), regulatory T cells) may predispose to a Th2 phenotype [88]. Psychological stress has been associated with increased proportions of both natural killer (NK) and NKT cells as well as the altering their functional mechanisms [89, 90].…”