Neuroimmunoendocrine circuitry of the ‘brain-skin connection’

Paus, Ralf; Theoharides, Theoharis C.; Arck, Petra C.

doi:10.1016/j.it.2005.10.002

Cited by 305 publications

(311 citation statements)

References 76 publications

(143 reference statements)

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“…The latter study, however, showed that this effect is dependent on the genotype of the mice used for testing, e.g., in C57BL6/J mice, a pigmentary effect of the POMC-KO is absent, likely due to the fact that this strain is recessive for agouti protein (Slominski et al, 2005a). Other cutaneous abnormalities in POMC-KO mice (including those of hair follicle cycling and the hair follicle immune system (Paus et al, 2006) still remain to be systematically explored.…”

Section: Discussionmentioning

confidence: 98%

Differential expression of HPA axis homolog in the skin

Slominski

Wortsman

Tuckey

et al. 2007

Molecular and Cellular Endocrinology

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SummaryHuman skin expresses elements of the hypothalamo-pituitary-adrenal (HPA) axis including proopiomelanocortin (POMC), corticotropin releasing hormone (CRH), the CRH receptor-1 (CRH-R1), key enzymes of corticosteroid synthesis and synthesizes glucocorticoids. Expression of these elements is organized in functional, cell type-specific regulatory loops, which imitate the signaling structural hierarchy of the HPA axis. In melanocytes and fibroblasts CRH-induced CRH-R1 stimulation upregulates POMC expression and production of ACTH through activation of cAMP dependent pathway(s). Melanocytes respond with enhanced production of cortisol and corticosterone, which is dependent on POMC activity. Fibroblasts respond to CRH and ACTH with enhanced production of corticosterone, but not cortisol, which is produced constitutively. Organcultured human scalp hair follicles also show a fully functional HPA axis equivalent, including cortisol synthesis and secretion and negative feedback regulation by cortisol on CRH expression. Thus differential, CRH-driven responses of skin reproduce key features of the central HPA axis at the tissue/single cell levels.

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Section: Discussionmentioning

confidence: 98%

Differential expression of HPA axis homolog in the skin

Slominski

Wortsman

Tuckey

et al. 2007

Molecular and Cellular Endocrinology

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259

267

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“…HF immune privilege, connective tissue sheath (CTS) mast cell degranulation. (see Arck et al, 2005a; Bodó et al, 2005 and2007; Botchkarev et al, 2004; Colombe et al., 2007; Deplewski and Rosenfield, 2000;Hasse et al, 2007; Kauser et al, 2006;Ohnemus et al, 2006;Paus et al, 2006;Peters et al, 2006b and2007;Philp et al, 2004;Slominski et al, 2007;Telek et al, 2007;Zouboulis et al, 2007) While this remains to be conclusively demonstrated, it is likely that HFeSC are fully integrated into this neuroendocrine tapestry of general HF biology. However, all we have to go by currently are some pointers to potentially important elements in the as yet obscure neuroendocrinology of HFeSC.…”

Section: Page 4 Of 38mentioning

confidence: 99%

(Neuro-)endocrinology of epithelial hair follicle stem cells

Paus

Arck

Tiede

2008

Molecular and Cellular Endocrinology

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The hair follicle is a repository of different types of somatic stem cells. However, even though the hair follicle is both a prominent target organ and a potent, non-classical site of production and/or metabolism of numerous polypetide-and steroid hormones, neuropeptides, neurotransmitters and neurotrophins, the (neuro-) endocrine controls of hair follicle epithelial stem cell (HFeSC) biology remain to be systematically explored.Focussing on HFeSCs, we attempt here to offer a "roadmap through terra incognita" by listing key open questions, by exploring endocrinologically relevant HFeSC gene profiling and mouse genomics data, and by sketching several clinically relevant pathways via which systemic and/or locally generated (neuro-)endocrine signals might impact on HFeSC. Exemplarily, we discuss e.g. the potential roles of glucocorticoid and vitamin D receptors, the hairless gene product, thymic hormones, bone morphogenic proteins (BMPs) and their antagonists, and Skg-3 in HFeSC biology. Furthermore, we elaborate on the potential role of nerve growth factor (NGF) and substance P-dependent neurogenic inflammation in HFeSC damage, and explore how neuroendocrine signals may influence the balance between maintenance and destruction of hair follicle immune privilege, which protects these stem cells and their progeny. These considerations call for a concerted research effort to dissect the (neuro)-endocrinology of HFeSCs much more systematically than before. The hair follicle (HF) and its special, associated mesenchyme (i.e. the connective tissue sheath, CTS) are repositories of different types of somatic stem cells (epithelial, mesenchymal, neural, mesenchymal) (Cotsarelis, 2006; Kruse et al., 2006;Millar, 2005;Ohyama et al., 2006;Tiede et al. 2007;Waters et al., 2007;Yu et al., 2006). These HFassociated stem cell populations are critical for HF development and function, including HF pigmentation (Nishimura et al., 2002(Nishimura et al., , 2005Sarin and Artandi, 2007). Fig. 1 shows several important, recognized hair follicle-associated stem cell populations and their bestcharacterized location(s) in the pilosebaceous unit, though it must be kept in mind that the indicated ones are unlikely to be the only stem cell population associated with mammalian skin appendages (Tiede et al. 2007). Clinical importance of hair follicle stem cellsHair follicle epithelial stem cells (HFeSCs) are clinically important, since they can be key targets for pathological processes, such as an autoaggressive inflammatory cell attack on HFeSC, e.g. in lupus erythematosus or lichen planopilaris, where the destruction of bulge HFeSCs (see Fig.1) abolishes the hair follicle's capacity to cycle and to rhythmically regenerate itself, leading to scarring alopecia (Cotsarelis, 2006;Hiroi et al., 2006;Mobini et al., 2005;Paus, 2006). Likewise, a gradual loss of HF melanocyte stem cells may exhaust the HF pigmentary unit's capacity to generate itself and to produce melanin and thus likely plays a key role in hair graying (Commo et al., 2004;...

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“…These molecules are mostly released from various cell types of the skin which are in close proximity to or even in direct physical contact with sensory nerve endings [48][49][50][51]. These mediators stimulate and/or sensitize the itch-selective sensory afferent fibers hence evoking action potential firing.…”

Section: Pruritogensmentioning

confidence: 99%

“…Therefore, via these interactions, alterations in the general condition and homeostatic balance of the skin (e.g. barrier function, inflammatory responses) may significantly affect the release of pruritogens and hence may induce itch [8,41,[51][52][53]. Since TRP channels play pivotal roles in these epithelial-neuronal interactions (see below), first we shortly summarize the roles of the most important pruritogen mediators and their related cellular mechanisms involved in itch sensation.…”

Section: Pruritogensmentioning

confidence: 99%

“…Beyond histamine, mast cells may also release several other (mostly inflammatory) mediators which process can be also triggered by SP or vasointestinal polypeptide [78]. These mast cell-derived mediators may, in turn, further activate sensory neurons resulting in further SP liberation [41,49,[51][52][53]. Participating in this "positive feedback," SP can be considered as an important etiological factor of itch in several diseases.…”

Section: Role Of Neuropeptides and Neurotrophinsmentioning

confidence: 99%

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TRP Channels and Pruritus

Tóth¹,

Bı́ró²

2013

TOPAINJ

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Itch (pruritus) is one of the most often seen sensory phenomena in clinical practice. Recent neurophysiological findings proposed the existence of a novel pruriceptive system which includes a multitude of pruritogenic (itch-inducing) peripheral mediators, itch-selective pruriceptors, sensory afferent networks, spinal cord neurons, and certain central nervous system regions. In this review, we first introduce major features of the pruriceptive system. We then focus on defining the roles of transient receptor potential (TRP) ion channels in skin-coupled itch and provide compelling evidence that certain thermosensitive TRP channels (especially TRPV1, TRPV3, TRPV4, and TRPA1) are indeed key players in pruritus pathogenesis. Finally, we propose TRP-centered future experimental directions towards the therapeutic targeting of TRP channels in the clinical management of itch.

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Neuroimmunoendocrine circuitry of the ‘brain-skin connection’

Cited by 305 publications

References 76 publications

Differential expression of HPA axis homolog in the skin

Differential expression of HPA axis homolog in the skin

(Neuro-)endocrinology of epithelial hair follicle stem cells

TRP Channels and Pruritus

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