Gene transcription of pro‐inflammatory cytokines and chemokines induced by IL ‐17A in canine keratinocytes

Canine atopic dermatitis (cAD) is a genetically inherited clinical syndrome that encompasses a diversity of mechanisms and can have a variety of triggers. Development of clinical disease is the result of genetic factors and environmental conditions, which shape the resulting immunological response. Clinical disease becomes evident once a threshold of inflammatory response is achieved. Skin barrier impairment plays a role in promoting cutaneous dysbiosis and increased allergen penetration. Keratinocytes shape the response of dendritic cells and subsequent lymphocytic response. Thymic stromal lymphopoietin is one of the links between the damaged skin barrier and the modulation of a T‐helper (Th)2 response. It is still unclear whether mutations in skin barrier genes exist in atopic dogs, as they do in humans, or whether the observed alterations are purely secondary to inflammation. A dysregulated immune response with increased Th2, Th17 and CD4+ CD25+ regulatory T cells has been reported. A variety of cytokines [interleukin(IL)‐31, IL‐34, Macrophage migration inhibitory factor] are proposed as potential biomarkers and treatment targets because they are increased in the serum of atopic dogs when compared to controls, although a correlation between serum levels of these factors and severity of disease is not always present. The main issue with many published studies is that atopic dogs are always only compared to normal controls. Thus, it is unclear whether the changes that we find are truly a signature of cAD or merely a manifestation of nonspecific broad inflammatory responses. Studies considering comparison with other inflammatory diseases different from cAD are urgently needed to correctly identify what is specific to this complicated syndrome.

Section: The Role Of the Microbial Composition Of Atopic Skinmentioning

confidence: 99%

Advances in our understanding of canine atopic dermatitis

Marsella

2021

“…Real-time RT-PCR was performed on genes encoding canine IL-4, IL-5, IL-13, INF-c and TNF-a using Thermal Cycler Dice Real-Time System II (Takara Bio Inc.) and SYBR Premix Ex Taq II (Takara Bio Inc.). 15,16 Three canine genes, CG14980, RPL32 and RPS18, were selected as reference genes. 16 PCR reactions were performed at 95°C for 10 s, followed by 47 cycles at 95°C for 5 s and 60°C for 30 s, with a final extension at 95°C for 15 s, 60°C for 30 s and 95°C for 15 s. The relative expression ratio was measured using the comparative threshold cycle (Ct) and the 2 -DDCt method.…”

Section: Real-time Qrt-pcrmentioning

confidence: 99%

Narrow‐band ultraviolet B therapy attenuates cutaneous T‐cell responses in hapten‐induced, experimental contact dermatitis in beagles

Onishi-Sakamoto

Makishi

Takami

et al. 2021

Self Cite

Background In human medicine, narrow‐band ultraviolet B (NB‐UVB) phototherapy has been used to treat various T‐cell‐mediated skin diseases. However, the effect of NB‐UVB on inflamed canine skin remains uncertain. Objectives To investigate the effect of NB‐UVB phototherapy on the skin of dogs with hapten‐induced contact dermatitis. Animals Seven healthy beagles without skin problems. Methods and materials Dogs were irradiated with varying doses of NB‐UVB to determine the minimal erythema dose (MED). After determining the MEDs of six dogs (excluding one of the seven whose skin did not show a visible reaction), we investigated the effect of NB‐UVB on their inflamed skin by topically applying 2,4‐dinitrochlorobenzene (DNCB), which causes type 1 helper T cell (Th1)‐ and cytotoxic T‐cell (Tc)1‐induced skin inflammation. We then irradiated the skin with NB‐UVB. We analysed the treated skin samples via histopathological and immunohistochemical methods, and TdT‐mediated dUTP nick‐end labelling (TUNEL) to demonstrate apoptotic cells. We also analysed the cytokine gene transcription via real‐time quantitative reverse transcription PCR. Results The NB‐UVB MEDs caused mild inflammatory changes yet no severe epidermal exfoliations in the irradiated skin. In DNCB‐treated skin irradiated by the NB‐UVB MEDs, TUNEL‐positive dermal apoptotic cells were increased significantly compared with those of DNCB‐treated, nonirradiated skin. INF‐γ and TNF‐α transcription levels in DNCB‐treated, irradiated skin were significantly lower than those in the DNCB‐treated, nonirradiated skin. Conclusion and clinical relevance Phototherapy using NB‐UVB MEDs attenuated cutaneous Th1 and Tc1 cytokine responses with minimal skin damage in a canine model of hapten‐induced contact dermatitis.

“…These results suggest that GM‐CSF production in CPEK activated via PAR‐2 may be regulated not only by NFAT, but also by another transcription factor, such as nuclear factor‐kB (NF‐kB) or activator protein‐1 (AP‐1). A recent study demonstrated that IL‐17A, a typical Th17 cytokine, also induced the transcription of gm‐csf in CPEK . A number of clinical trials targeting GM‐CSF are underway in humans with rheumatoid arthritis, multiple sclerosis, asthma and plaque psoriasis, but not AD …”

Section: Keratinocyte‐derived Chemokines and Cytokines That Are Direcmentioning

confidence: 99%

“…A recent study demonstrated that IL-17A, a typical Th17 cytokine, also induced the transcription of gm-csf in CPEK. 95 A number of clinical trials targeting GM-CSF are underway in humans with rheumatoid arthritis, multiple sclerosis, asthma and plaque psoriasis, but not AD. 86 Thymic stromal lymphopoietin (TSLP) Thymic stromal lymphopoietin (TSLP) was first identified as a stimulator of B cell development in the culture supernatant of a murine thymic stromal cell line.…”

Section: Keratinocyte-derived Cytokines and Chemokinesmentioning

confidence: 99%

A review of the roles of keratinocyte‐derived cytokines and chemokines in the pathogenesis of atopic dermatitis in humans and dogs

Asahina

Maeda

2016

Self Cite