The junctional adhesion molecule-like protein (JAML) is important for the inflammatory response during contact hypersensitivity
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The junctional adhesion molecule-like protein (JAML) is important for the inflammatory response during contact hypersensitivity. / Mraz, Veronika; Lohmann, Rebecca K.D.; Menzel, Mandy; Hawkes, Alana; Vaher, Helen; Funch, Anders B.; Jee, Mia H.; Gadsbøll, Anne Sofie Ø.; Weber, Julie F.; Yeung, Kelvin; Ødum, Niels; Woetmann, Anders; McKay, Dianne; Witherden, Deborah; Geisler, Carsten; Bonefeld, Charlotte M.
In: Contact Dermatitis, Vol. 89, No. 5, 2023, p. e63-e65.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The junctional adhesion molecule-like protein (JAML) is important for the inflammatory response during contact hypersensitivity
AU - Mraz, Veronika
AU - Lohmann, Rebecca K.D.
AU - Menzel, Mandy
AU - Hawkes, Alana
AU - Vaher, Helen
AU - Funch, Anders B.
AU - Jee, Mia H.
AU - Gadsbøll, Anne Sofie Ø.
AU - Weber, Julie F.
AU - Yeung, Kelvin
AU - Ødum, Niels
AU - Woetmann, Anders
AU - McKay, Dianne
AU - Witherden, Deborah
AU - Geisler, Carsten
AU - Bonefeld, Charlotte M.
N1 - Publisher Copyright: © 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.
PY - 2023
Y1 - 2023
N2 - Background: The junctional adhesion molecule-like protein (JAML) plays important roles in wound healing and activation of epidermal γδ T cells in mice. Whether JAML plays a role in contact hypersensitivity (CHS), the animal model of allergic contact dermatitis (ACD), is not known. Methods: To examine the role of JAML in CHS, we used various mouse models of CHS in JAML knockout (KO) and wild-type (WT) mice. Furthermore, the expression of the JAML ligand coxsackievirus and adenovirus receptor (CXADR) on keratinocytes was accessed in vitro and in vivo. Results: JAML KO mice had a diminished inflammatory response during both the sensitization and elicitation phase of CHS and had reduced numbers of CD8+ and CD4+ T cells in the epidermis. Furthermore, interferon γ (IFNγ), interleukin 1β (IL-1β) and CXCL10 production were significantly reduced in JAML KO mice during the elicitation phase. We found that CD8+ T cells express JAML and that JAML is essential for rapid flare-up responses to contact allergens. Finally, we show that keratinocytes up-regulate the JAML ligand CXADR following exposure to contact allergens. Conclusion: Our study is the first to show a central role of JAML in CHS and reveals a potential new target for the treatment of ACD in humans.
AB - Background: The junctional adhesion molecule-like protein (JAML) plays important roles in wound healing and activation of epidermal γδ T cells in mice. Whether JAML plays a role in contact hypersensitivity (CHS), the animal model of allergic contact dermatitis (ACD), is not known. Methods: To examine the role of JAML in CHS, we used various mouse models of CHS in JAML knockout (KO) and wild-type (WT) mice. Furthermore, the expression of the JAML ligand coxsackievirus and adenovirus receptor (CXADR) on keratinocytes was accessed in vitro and in vivo. Results: JAML KO mice had a diminished inflammatory response during both the sensitization and elicitation phase of CHS and had reduced numbers of CD8+ and CD4+ T cells in the epidermis. Furthermore, interferon γ (IFNγ), interleukin 1β (IL-1β) and CXCL10 production were significantly reduced in JAML KO mice during the elicitation phase. We found that CD8+ T cells express JAML and that JAML is essential for rapid flare-up responses to contact allergens. Finally, we show that keratinocytes up-regulate the JAML ligand CXADR following exposure to contact allergens. Conclusion: Our study is the first to show a central role of JAML in CHS and reveals a potential new target for the treatment of ACD in humans.
KW - contact hypersensitivity
KW - CXADR
KW - epidermal-resident memory T cell
KW - JAML
U2 - 10.1111/cod.14409
DO - 10.1111/cod.14409
M3 - Journal article
C2 - 37619972
AN - SCOPUS:85168669425
VL - 89
SP - e63-e65
JO - Contact Dermatitis
JF - Contact Dermatitis
SN - 0105-1873
IS - 5
ER -
ID: 368671889