Serum canine thymus and activation‐regulated chemokine (TARC/CCL17) concentrations correlate with disease severity and therapeutic responses in dogs with atopic dermatitis

Asahina, Ryota; Ueda, Kazunori; Oshima, Yuri; Kanei, Toshitaka; Kato, Masahiro; Furue, Masutaka; Tsukui, Toshihiro; Nagata, Masahiko; Maeda, Sadatoshi

doi:10.1111/vde.12894

Cited by 12 publications

(24 citation statements)

References 44 publications

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“…We lack conclusive evidence of a causative effect of skin barrier dysfunction in the actual development of cAD, although in vitro studies using atopic keratinocytes showed that the behaviour of the keratinocytes between normal and atopic dogs is different in terms of growth and ability to establish connections. 8,9 Many of the initial studies in veterinary medicine have been observational studies of associations. 10 Associations are not the same as causation and it is necessary to work out how critical skin barrier impairment is per se in the actual causation of the canine disease.…”

Section: The Importance Of the Skin Barriermentioning

confidence: 99%

Advances in our understanding of canine atopic dermatitis

Marsella

2021

Veterinary Dermatology

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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.

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Section: The Importance Of the Skin Barriermentioning

confidence: 99%

Advances in our understanding of canine atopic dermatitis

Marsella

2021

Veterinary Dermatology

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“…Furthermore, the chemokine CCL17 was significantly increased in dogs with canine atopic dermatitis. Dogs treated successfully with prednisolone or oclacitinib showed a decrease in CCL17 but a direct effect of prednisolone on chemokine release remained debatable [ 106 ].…”

Section: Resultsmentioning

confidence: 99%

Methylprednisolone Induces Extracellular Trap Formation and Enhances Bactericidal Effect of Canine Neutrophils

Steffensen

Imker

Lassnig

et al. 2021

IJMS

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Methylprednisolone is a glucocorticoid and can negatively influence immune defense mechanisms. During bacterial infections in the dog, neutrophils infiltrate infected tissue and mediate antimicrobial effects with different mechanisms such as phagocytosis and neutrophil extracellular trap (NET) formation. Here, we investigated the influence of methylprednisolone on canine NET formation and neutrophil killing efficiency of Gram positive and Gram negative bacteria. Therefore, canine blood derived neutrophils were treated with different concentrations of methylprednisolone over time. The survival factor of Staphylococcus pseudintermedius, Streptococcus canis or Escherichia coli was determined in presence of stimulated neutrophils. Additionally, free DNA and nucleosomes as NET marker were analyzed in supernatants and neutrophils were assessed for NET formation by immunofluorescence microscopy. Methylprednisolone concentrations of 62.5 and 625 µg/mL enhanced the neutrophil killing of Gram positive bacteria, whereas no significant influence was detected for the Gram negative Escherichia coli. Interestingly, higher amounts of free DNA were detected under methylprednisolone stimulation in a concentration dependency and in the presence of Streptococcus canis and Escherichia coli. The nucleosome release by neutrophils is induced by bacterial infection and differs depending on the concentration of methylprednisolone. Furthermore, immunofluorescence microscopy analysis identified methylprednisolone at a concentration of 62.5 µg/mL as a NET inducer. In summary, methylprednisolone enhances NET-formation and time-dependent and concentration-dependent the bactericidal effect of canine neutrophils on Gram positive bacteria.

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“…reported that atopic dogs have a significantly higher expression of CCL17 when compared to healthy dogs using a custom‐made ELISA. The magnitude of expression was in the order of ng/mL for atopic dogs and pg./mL for healthy dogs 6 . Atopic dogs also had a variable CADESI‐04 score ranging from 0 to 117 and a median of 12 6 .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of cutaneous and circulating (serum and exosomes) levels of chemokines (CCL17, CCL22, CCL27 and CCL28) in atopic dogs and their correlation with severity of the disease

Santoro

Archer

Chong

2022

Veterinary Dermatology

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Background Canine atopic dermatitis (AD) is a complex multifactorial disease characterised by an exaggerated immunological response. Little is known about the role that cutaneous and circulating chemokines play in disease severity. Objective To evaluate the messenger (m)RNA and protein levels of selected chemokines in skin and serum of healthy and atopic dogs, and in the atopic group to determine whether there is a correlation with disease severity. Materials and methods Skin biopsies and blood samples were taken from 12 privately owned atopic [lesional (AD‐L) and nonlesional (AD‐NL) skin] and 12 privately owned healthy dogs. Circulating exosomes were extracted from the serum. Cutaneous and exosomal mRNA levels of CCL17, CCL22, CCL27 and CCL28 were quantified using quantitative real‐time PCR. Protein levels were evaluated using canine‐specific ELISA kits. The severity and extent of the clinical signs also were assessed in the atopic dogs using Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI‐04) and a validated pruritus Visual Analog Scale (pVAS). Results The expression of CCL28 exosomes in skin was greater in AD‐L when compared to healthy (P = 0.019) and AD‐NL (P = 0.002) samples. However, serum expression was lower in dogs with AD compared to healthy dogs (P = 0.03). A higher expression of CCL17 and CCL22 was seen in AD‐L when compared to healthy skin (P = 0.018 and P = 0.019, respectively). There also was a positive correlation between clinical scores and CCL22 (AD‐NL; r = 0.6, P = 0.05) and between the pruritus score and CCL22 (AD‐L; r = 0.6, P = 0.05). Differences in CCL27 concentrations were not observed. Conclusions and clinical importance This study suggests that CCL17, CCL22 and CCL28 may play a role in the cutaneous inflammatory response in atopic dogs. They may be considered as markers of disease severity, although further studies are needed to validate these findings.

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Serum canine thymus and activation‐regulated chemokine (TARC/CCL17) concentrations correlate with disease severity and therapeutic responses in dogs with atopic dermatitis

Cited by 12 publications

References 44 publications

Advances in our understanding of canine atopic dermatitis

Advances in our understanding of canine atopic dermatitis

Methylprednisolone Induces Extracellular Trap Formation and Enhances Bactericidal Effect of Canine Neutrophils

Evaluation of cutaneous and circulating (serum and exosomes) levels of chemokines (CCL17, CCL22, CCL27 and CCL28) in atopic dogs and their correlation with severity of the disease

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