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Investigating the Role of Interleukin-31 in an Experimental Model of Acute Canine Atopic Dermatitis.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Investigating the Role of Interleukin-31 in an Experimental Model of Acute Canine Atopic Dermatitis./
作者:	Mochizuki, Chie.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:	136 p.
附註:	Source: Dissertations Abstracts International, Volume: 83-06, Section: B.
Contained By:	Dissertations Abstracts International83-06B.
標題:	Infections. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28847839
ISBN:	9798759926443

Investigating the Role of Interleukin-31 in an Experimental Model of Acute Canine Atopic Dermatitis.
Mochizuki, Chie.

Investigating the Role of Interleukin-31 in an Experimental Model of Acute Canine Atopic Dermatitis. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 136 p.

Source: Dissertations Abstracts International, Volume: 83-06, Section: B.

Thesis (Ph.D.)--North Carolina State University, 2021.

This item must not be sold to any third party vendors.

Atopic dermatitis (AD) is a most common, chronically relapsing, allergic skin disease of humans and dogs. Recent studies have revealed that interleukin 31 (IL-31) represents one of the critical cytokines in human and canine AD, however, there are occasional failures of disease control with IL-31 inhibition, indicating that further researched are needed.In our first experiment (Chapter 2), we tested if the proactive administration of the anticanine IL-31 monoclonal antibody (mAb), lokivetmab (LKV), would prevent or delay flares of canine AD in experimental and clinical settings. Using our canine AD model, one injection of LKV prevented nearly all expected allergen-induced pruritus manifestations but not skin lesion development. In dogs with spontaneous AD, 28% of dogs did not exhibit an AD flare for at least one year while receiving LKV-monotherapy. On the other hand, the median time-to-flare after starting LKV-proactive therapy was only 63 days. This observation led to the hypothesis that IL31 has a minor role in skin lesion development in contrast to its central role in atopic itch, which might explain the insufficient effect of current strategies for inhibiting IL-31 to delay AD flares in some dogs.To have a better understanding of the role of IL-31 in the development of canine AD skin lesions, we assessed the chronology of the expression of IL-31 and determined the identity of cells producing IL-31 in experimental acute AD skin lesions of dogs (Chapter 3). We collected skin samples from four house-dust-mite (HDM)-experimentally-sensitized atopic dogs at 0, 24, 48 and 96 hours after allergen provocation. IL-31 single-staining immunofluorescence (IF), as well as IL-31/CD3 and IL-31/CD4 double-staining IF were performed. In three of four dogs, the highest numbers of IL-31-positive cells occurred at 24 or 48 hours, and it started to decrease at 96 hours. The majority of IL-31-positive cells co-expressed CD3 (range:91-100%) and CD4 (range:63-100%), indicating that they were helper T cells. Unexpectedly, sebaceous glands were strongly immunolabeled with IL-31; however, we could not detect IL31 mRNA in any sebaceous glands using the RNAscope method, thus could not yet confirm these cells as representing another novel cellular source of IL-31 (Chapter 4). These findings suggested an early and transient production of IL-31 by Th2 cells, supporting the concept of using IL-31 inhibiting LKV as a proactive therapy to prevent AD flares.These observations led to the hypothesis that other cytokines, independent of IL-31, are responsible for developing acute atopic inflammation and contribute to the treatment failures in IL-31-inhibiting therapy. In the final set of our studies (Chapter 5), we compared the cytokine transcriptome profiling in acute AD skin, with or without IL-31 inhibition by LKV. Skin samples were obtained from six HDM-experimentally-sensitized atopic dogs at 0, 6, 12, 24, 48 and 96 hours after allergen provocation. The results revealed no significant difference in the mRNA expression of major cytokines between with or without IL-31 inhibition. We also found that IL33, IL13, CCL17 and IL9, and potentially IL6 and CCL22, were still significantly upregulated despite a previous IL-31 inhibition, suggesting that these cytokines could be valuable targets for inhibition to supplement LKV therapy.

ISBN: 9798759926443Subjects--Topical Terms:

1621997
Infections.

Investigating the Role of Interleukin-31 in an Experimental Model of Acute Canine Atopic Dermatitis.
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520 $a Atopic dermatitis (AD) is a most common, chronically relapsing, allergic skin disease of humans and dogs. Recent studies have revealed that interleukin 31 (IL-31) represents one of the critical cytokines in human and canine AD, however, there are occasional failures of disease control with IL-31 inhibition, indicating that further researched are needed.In our first experiment (Chapter 2), we tested if the proactive administration of the anticanine IL-31 monoclonal antibody (mAb), lokivetmab (LKV), would prevent or delay flares of canine AD in experimental and clinical settings. Using our canine AD model, one injection of LKV prevented nearly all expected allergen-induced pruritus manifestations but not skin lesion development. In dogs with spontaneous AD, 28% of dogs did not exhibit an AD flare for at least one year while receiving LKV-monotherapy. On the other hand, the median time-to-flare after starting LKV-proactive therapy was only 63 days. This observation led to the hypothesis that IL31 has a minor role in skin lesion development in contrast to its central role in atopic itch, which might explain the insufficient effect of current strategies for inhibiting IL-31 to delay AD flares in some dogs.To have a better understanding of the role of IL-31 in the development of canine AD skin lesions, we assessed the chronology of the expression of IL-31 and determined the identity of cells producing IL-31 in experimental acute AD skin lesions of dogs (Chapter 3). We collected skin samples from four house-dust-mite (HDM)-experimentally-sensitized atopic dogs at 0, 24, 48 and 96 hours after allergen provocation. IL-31 single-staining immunofluorescence (IF), as well as IL-31/CD3 and IL-31/CD4 double-staining IF were performed. In three of four dogs, the highest numbers of IL-31-positive cells occurred at 24 or 48 hours, and it started to decrease at 96 hours. The majority of IL-31-positive cells co-expressed CD3 (range:91-100%) and CD4 (range:63-100%), indicating that they were helper T cells. Unexpectedly, sebaceous glands were strongly immunolabeled with IL-31; however, we could not detect IL31 mRNA in any sebaceous glands using the RNAscope method, thus could not yet confirm these cells as representing another novel cellular source of IL-31 (Chapter 4). These findings suggested an early and transient production of IL-31 by Th2 cells, supporting the concept of using IL-31 inhibiting LKV as a proactive therapy to prevent AD flares.These observations led to the hypothesis that other cytokines, independent of IL-31, are responsible for developing acute atopic inflammation and contribute to the treatment failures in IL-31-inhibiting therapy. In the final set of our studies (Chapter 5), we compared the cytokine transcriptome profiling in acute AD skin, with or without IL-31 inhibition by LKV. Skin samples were obtained from six HDM-experimentally-sensitized atopic dogs at 0, 6, 12, 24, 48 and 96 hours after allergen provocation. The results revealed no significant difference in the mRNA expression of major cytokines between with or without IL-31 inhibition. We also found that IL33, IL13, CCL17 and IL9, and potentially IL6 and CCL22, were still significantly upregulated despite a previous IL-31 inhibition, suggesting that these cytokines could be valuable targets for inhibition to supplement LKV therapy.
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