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

Abstract

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.

Cytokine transcriptome profiling in acute experimental canine atopic dermatitis skin lesions afterIL‐31 inhibition with lokivetmab

“…Based on their active gene expression levels and significant upregulation compared to their expression at baseline, we identified IL‐33, IL‐13, CCL17, and IL‐9, and potentially IL‐6 and CCL22, as possible targets for inhibition which might complement the action of LKV. To support this, the upregulation of mRNA or protein expression of IL‐33, IL‐13, and CCL17 has been reported in the skin or sera of client‐owned dogs with AD compared to healthy dogs in multiple studies 27–31 . Some of these cytokines and chemokines (e.g., IL‐33, CCL17, IL‐6, CCL22) are produced at a very early stage of AD acute flare induction, which is likely to be even before Th2 cells produce IL‐31 32 .…”

Canine Models of Inflammatory Skin Diseases and Their Application in Pharmacological Research

“…In the same study, the authors were able to show significantly decreased protein expression of CCL28 in the lesional skin, serum, and serum exosome of atopic dogs when compared with healthy controls (Santoro et al., 2022). Finally, the authors were able to show a negative correlation between the concentration of CCL28 in non‐lesional skin and the clinical severity of AD, as measured by the CADESI score, in atopic dogs (Santoro et al., 2022). In contrast, a positive correlation between serum exosomal TARC and the CADESI score was seen in atopic dogs (Santoro et al., 2022).…”

“…However, in a more recent study, using a commercially available ELISA kit for canine TARC, the authors were not able to detect a serum concentration of TARC in healthy or atopic dogs. Nevertheless, a non‐significantly different amount of TARC was present in the serum exosomes of healthy and atopic dogs (Santoro et al., 2022). In the same study, the authors were able to show significantly decreased protein expression of CCL28 in the lesional skin, serum, and serum exosome of atopic dogs when compared with healthy controls (Santoro et al., 2022).…”

“…Nevertheless, a non‐significantly different amount of TARC was present in the serum exosomes of healthy and atopic dogs (Santoro et al., 2022). In the same study, the authors were able to show significantly decreased protein expression of CCL28 in the lesional skin, serum, and serum exosome of atopic dogs when compared with healthy controls (Santoro et al., 2022). Finally, the authors were able to show a negative correlation between the concentration of CCL28 in non‐lesional skin and the clinical severity of AD, as measured by the CADESI score, in atopic dogs (Santoro et al., 2022).…”

Keloid Patient Plasma-Derived Exosomal hsa_circ_0020792 Promotes Normal Skin Fibroblasts Proliferation, Migration, and Fibrogenesis via Modulating miR-193a-5p and Activating TGF-β1/Smad2/3 Signaling

“…It has been shown that peripheral circulating blood exosomes are involved in the pathogenesis of various diseases including skin diseases. [26][27][28] CircRNAs have been found in exosomes derived from human blood samples with clinical implications. 29 In addition, circRNAs exert key roles in the occurrence and development of keloid.…”