The role of CD44 in cutaneous inflammation
Mona Man
Department of Dermatology, University of California School of Medicine, San Francisco, CA, USA;
Search for more papers by this authorPeter M. Elias
Department of Dermatology, University of California School of Medicine, San Francisco, CA, USA;
Search for more papers by this authorWenyan Man
Department of Dermatology, University of California School of Medicine, San Francisco, CA, USA;
Search for more papers by this authorYan Wu
Department of Dermatology, University of California School of Medicine, San Francisco, CA, USA;
Search for more papers by this authorLilly Y. W. Bourguignon
Dermatology and Medical Services (Metabolism), VAMC, San Francisco, CA, USA;
Department of Medicine, University of California School of Medicine, San Francisco, CA, USA;
Search for more papers by this authorKenneth R. Feingold
Department of Dermatology, University of California School of Medicine, San Francisco, CA, USA;
Dermatology and Medical Services (Metabolism), VAMC, San Francisco, CA, USA;
Department of Medicine, University of California School of Medicine, San Francisco, CA, USA;
Search for more papers by this authorMao-Qiang Man
Department of Dermatology, University of California School of Medicine, San Francisco, CA, USA;
Department of Dermatology, Zunyi Medical College, Guizhou, China
Search for more papers by this authorMona Man
Department of Dermatology, University of California School of Medicine, San Francisco, CA, USA;
Search for more papers by this authorPeter M. Elias
Department of Dermatology, University of California School of Medicine, San Francisco, CA, USA;
Search for more papers by this authorWenyan Man
Department of Dermatology, University of California School of Medicine, San Francisco, CA, USA;
Search for more papers by this authorYan Wu
Department of Dermatology, University of California School of Medicine, San Francisco, CA, USA;
Search for more papers by this authorLilly Y. W. Bourguignon
Dermatology and Medical Services (Metabolism), VAMC, San Francisco, CA, USA;
Department of Medicine, University of California School of Medicine, San Francisco, CA, USA;
Search for more papers by this authorKenneth R. Feingold
Department of Dermatology, University of California School of Medicine, San Francisco, CA, USA;
Dermatology and Medical Services (Metabolism), VAMC, San Francisco, CA, USA;
Department of Medicine, University of California School of Medicine, San Francisco, CA, USA;
Search for more papers by this authorMao-Qiang Man
Department of Dermatology, University of California School of Medicine, San Francisco, CA, USA;
Department of Dermatology, Zunyi Medical College, Guizhou, China
Search for more papers by this authorAbstract
Abstract: CD44 is a transmembrane glycoprotein expressed in various tissues including the skin. Previous studies indicated that CD44 is required for epidermal permeability barrier homeostasis and keratinocyte differentiation. Yet, while some studies have demonstrated that CD44 is critical for the development of inflammation, others have shown that CD44 is not essential for the development of cutaneous inflammation. In this study, we evaluated the changes in epidermal CD44 expression in a variety of skin inflammatory models and determined whether CD44 is required for the development of cutaneous inflammation. Inflammatory responses were compared in CD44 KO versus wild-type mice in acute models of irritant and allergic contact dermatitis, as well as in a subacute allergic contact dermatitis induced by repeated hapten treatment. Inflammatory responses were assessed by measuring ear thickness and epidermal hyperplasia in haematoxylin & eosin-stained sections. Our results demonstrate that: (i) epidermal CD44 expression increases in both acute and subacute cutaneous inflammatory models; and (ii) acute disruption of the epidermal permeability barrier function increases epidermal CD44 expression. Whereas inflammatory responses did not differ between CD44 KO and wild-type mice in acute models of irritant and allergic contact dermatitis, both inflammatory responses and epidermal hyperplasia increased in CD44 KO mice following repeated hapten challenges. These results show first, that permeability barrier disruption and inflammation stimulate epidermal CD44 expression, and second, that CD44 modulates epidermal proliferation and inflammatory responses in a subacute murine allergic contact dermatitis model.
Supporting Information
Figure S1. No Difference in Cutaneous IL-1α Expression Between CD44 KO And Wild Type Mice in Acute Contact Dermatitis Models: Ear inflammation was induced by topical TPA or oxazolone treatment as described in the methods section. Ear samples were obtained 20 h after TPA or the last oxazolone application. No significant difference in IL-1α expression was seen between CD44 KO and wild type mice (supplemental figure 1c vs. d; e vs. f). Supplemental figure 1a is normal skin from wild type mice and b is normal skin from CD44 KO mice. Supplemental figure 1c and d are acute dermatitis induced by topical oxazolone in wild type and CD44 KO mice, respectively. Supplemental figure 1e and f are acute dermatitis induced by topical TPA in wild type and CD44 KO mice, respectively. Supplemental figure 1g is negative control. The magnifications are the same for all pictures. Scale Bar = 20 μm.
Figure S2. Increased TCR Vβ8.1-3 Cell Infiltration in CD44 KO Mice in Subacute Allergic Dermatitis Models: Subacute allergic dermatitis was induced as described in the methods section. Skin samples were taken 24 h after the last oxazolone treatment. TCR Vβ8.1-3 staining was performed as described in the methods section and pictures were taken with a microscope, equipped with AxioVision software 3.1. There were 4 mice for each treatment group. Figures shown are representative. Scale bar = 20 μm.
Figure S3. Increased Dermal IL-1α Expression in CD44 KO Mice in Subacute Allergic Dermatitis Models: Subacute allergic dermatitis was induced as described in the methods section. Skin samples were taken 24 h after the last oxazolone treatment. IL-1α expression was determined as described in the methods section and pictures were taken with a microscope, equipped with AxioVision software 3.1. There were 4 mice for each treatment group. Figures shown are representative. Scale bar = 20 μm.
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