Biological clock dysfunction exacerbates contact hypersensitivity in mice

Takita, E.; Yokota, Shigeru; Tahara, Yu; Hirao, Akiko; Aoki, Natsumi; Nakamura, Yuki; Nakao, Akihiro; Shibata, Shigenobu

doi:10.1111/j.1365-2133.2012.11176.x

Cited by 46 publications

(41 citation statements)

References 29 publications

(41 reference statements)

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“…This suggests that the mechanisms underlying memory T cell dependent skin inflammatory responses are impaired following loss of CNS circadian rhythmicity. This outcome stands in contrast with a report of enhanced contact hypersensitivity (CHS) responses in Clock -/- mice (Takita et al, 2013). However, plasma corticosterone (B) concentrations are markedly reduced in Clock -/- mice, and effects of this genotype on CHS are eliminated by B or dexamethasone treatment (Takita et al, 2013), suggesting that the immunophenotype is likely mediated by a pleiotropic effect of CLOCK on neuroendocrine function.…”

Section: Discussioncontrasting

confidence: 99%

Impaired leukocyte trafficking and skin inflammatory responses in hamsters lacking a functional circadian system

Prendergast

Cable

Patel

et al. 2013

Brain, Behavior, and Immunity

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The immune system is under strong circadian control, and circadian desynchrony is a risk factor for metabolic disorders, inflammatory responses and cancer. Signaling pathways that maintain circadian rhythms (CRs) in immune function in vivo, and the mechanisms by which circadian desynchrony impairs immune function, remain to be fully-identified. These experiments tested the hypothesis that the hypothalamic circadian pacemaker in the suprachiasmatic nucleus (SCN) drives CRs in the immune system, using a non-invasive model of SCN circadian arrhythmia. Robust CRs in blood leukocyte trafficking, with a peak during the early light phase (ZT4) and nadir in the early dark phase (ZT18), were absent in arrhythmic hamsters, as were CRs in spleen clock gene (per1, bmal1) expression, indicating that a functional pacemaker in the SCN is required for the generation of CRs in leukocyte trafficking and for driving peripheral clocks in secondary lymphoid organs. Pinealectomy was without effect on CRs in leukocyte trafficking, but abolished CRs in spleen clock gene expression, indicating that nocturnal melatonin secretion is necessary for communicating circadian time information to the spleen. CRs in trafficking of antigen presenting cells (CD11c+ dendritic cells) in the skin were abolished, and antigen-specific delayed-type hypersensitivity skin inflammatory responses were markedly impaired in arrhythmic hamsters. The SCN drives robust CRs in leukocyte trafficking and lymphoid clock gene expression; the latter of which is not expressed in the absence of melatonin. Robust entrainment of the circadian pacemaker provides a signal critical to diurnal rhythms in immunosurveilliance and optimal memory T-cell dependent immune responses.

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Section: Discussioncontrasting

confidence: 99%

Impaired leukocyte trafficking and skin inflammatory responses in hamsters lacking a functional circadian system

Prendergast

Cable

Patel

et al. 2013

Brain, Behavior, and Immunity

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“…We have previously shown that Clock Δ19/Δ19 mice exhibit significantly severe levels of allergic contact dermatitis compared with wild-type mice, where the mice were treated with TNCB (2,4,6-trinitro-1-chlorobenzene) on the abdominal skin on day 0 (sensitization) and then with TNCB on the ears on day 5 (challenge) (Takita et al, 2013). The exaggerated allergic contact dermatitis phenotypes in Clock Δ19/Δ19 mice were associated with increased Th2-type responses such as serum IgE levels and mast cell number in the skin.…”

Section: Discussionmentioning

confidence: 99%

Circadian gene clock regulates psoriasis-like skin inflammation in mice

Ando

Nakamura

Aoki

et al. 2016

Journal of Dermatological Science

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There are several reports suggesting that the pathophysiology of psoriasis may be associated with aberrant circadian rhythms. However, the mechanistic link between psoriasis and the circadian time-keeping system, "the circadian clock," remains unclear. This study determined whether the core circadian gene, Clock, had a regulatory role in the development of psoriasis. For this purpose, we compared the development of psoriasis-like skin inflammation induced by the Toll-like receptor 7 ligand imiquimod (IMQ) between wild-type mice and mice with a loss-of-function mutation of Clock. We also compared the development of IMQ-induced dermatitis between wild-type mice and mice with a loss-of-function mutation of Period2 (Per2), another key circadian gene that inhibits CLOCK activity. We found that Clock mutation ameliorated IMQ-induced dermatitis, whereas the Per2 mutation exaggerated IMQ-induced dermatitis, when compared with wild-type mice associated with decreased or increased IL-23 receptor (IL-23R) expression in γ/δ + T cells, respectively. In addition, CLOCK directly bound to the promoter of IL-23R in γ/δ + T cells, and IL-23R expression in the mouse skin was under circadian control. These findings suggest that Clock is a novel regulator of psoriasis-like skin inflammation in mice via direct modulation of IL-23R expression in γ/δ + T cells, establishing a mechanistic link between psoriasis and the circadian clock.

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“…An intrinsic daily physiological rhythm called circadian rhythm is thought to affect the immune system. Several experimental studies have demonstrated that mutation in the circadian clock genes greatly affects immune responses [104][105][106]. Immune tolerance development is closely associated with the onset of immunological disorders.…”

Section: Circadian Rhythmsmentioning

confidence: 99%

Atopic Dermatitis: Identification and Management of Complicating Factors

Tamagawa‐Mineoka

Katoh

2020

IJMS

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Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease, associated with impaired skin barrier function and an atopic background. Various complicating factors, such as irritants, aeroallergens, food, microbial organisms, contact allergens, sweat, and scratching can induce the development of AD symptoms. Irritants, including soap/shampoo and clothes, can cause itching and eczematous lesions. In addition, young children with AD tend to become sensitized to eggs, milk, or peanuts, while older children and adults more often become sensitized to environmental allergens, such as house dust mites (HDM), animal dander, or pollen. Serum-specific IgE levels and skin prick test reactions to food tend to show high negative predictive values and low specificity and positive predictive values for diagnosing food allergy. On the other hand, AD adult patients tend to have severe skin symptoms and exhibit high HDM-specific IgE levels. Microbial organisms, e.g., Staphylococcus aureus and Malassezia furfur, might contribute to the pathogenetic mechanisms of AD. While sweat plays a major role in maintaining skin homeostasis, it can become an aggravating factor in patients with AD. Furthermore, scratching often exacerbates eczematous lesions. Several patient-specific complicating factors are seen in most cases. The identification and management of complicating factors are important for controlling AD.

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Biological clock dysfunction exacerbates contact hypersensitivity in mice

Abstract: The present results suggest that circadian rhythm might be an important factor in the regulation of CHS via corticosterone rhythmicity and/or level.

Cited by 46 publications

References 29 publications

Impaired leukocyte trafficking and skin inflammatory responses in hamsters lacking a functional circadian system

Impaired leukocyte trafficking and skin inflammatory responses in hamsters lacking a functional circadian system

Circadian gene clock regulates psoriasis-like skin inflammation in mice

Atopic Dermatitis: Identification and Management of Complicating Factors

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