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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. [ABSTRACT FROM AUTHOR]

Moderate paddling, as in long distance kayaking, constitutes an endurance activity, which shares energetic aspects with activities such as long distance running and road cycling. The aim of the present study was to investigate whether in moderate paddling there is a U-shaped relationship between oxygen uptake and stroke rate, and also whether elite kayakers apply a freely chosen stroke rate, which is energetically optimal. Eleven young male elite kayakers performed moderate kayak ergometry at preset target stroke rates of 65, 75, and 90 strokes min-1, and at a freely chosen stroke rate, while physiological responses including oxygen uptake were measured. The results showed that considering average values calculated across all participants, there was an approximately U-shaped relationship between oxygen uptake and target stroke rate with a minimum at 75 strokes min-1. The freely chosen stroke rate was 67.0 ± 6.1 strokes min-1. Thus, the freely chosen stroke rate, for the group in total, appeared to be lower and require higher oxygen uptake as compared to the energetically optimal preset target stroke rate. Eight out of 11 participants had a higher oxygen uptake (5.1% ± 6.7%, p = 0.028, across all participants) at their freely chosen stroke rate than at the preset target stroke rate, which resulted in the lowest oxygen uptake. In conclusion, an approximately U-shaped relationship between oxygen uptake and stroke rate for young elite kayakers during moderate ergometer kayaking was found. Additionally, the freely chosen stroke rate was systematically lower and, consequently, required higher oxygen uptake than the preset stroke rate, which resulted in the lowest oxygen uptake. [ABSTRACT FROM AUTHOR]

Background: Allergic contact dermatitis (ACD) is classically described as a delayed‐type hypersensitivity reaction. However, patients often experience flare‐ups characterized by itching erythema, edema, and often vesicles occurring within hours after re‐exposure of previously sensitized skin to the specific contact allergen. Recent studies have indicated that skin‐resident memory T (TRM) cells play a central role in ACD. However, the pathogenic role of TRM cells in allergen‐induced flare‐ups is not known. Methods: By the use of various mouse models and cell depletion protocols, we investigated the role of epidermal TRM cells in flare‐up reactions to the experimental contact allergen 1‐fluoro‐2,4‐dinitrobenzene. The inflammatory response was measured by changes in ear thickness, and the cellular composition in epidermis was determined by flow cytometry and confocal microscopy. Finally, adaptive transfer and inhibitors were used to determine the role of TRM cells, neutrophils, and CXCL1/CXCL2 in the response. Results: We show that CD8+ TRM cells initiate massive infiltration of neutrophils in the epidermis within 12 h after re‐exposure to the contact allergen. Depletion of neutrophils before re‐exposure to the allergen abrogated the flare‐up reactions. Furthermore, we demonstrate that CD8+ TRM cells mediate neutrophil recruitment by inducing CXCL1 and CXCL2 production in the skin, and that blockage of the C‐X‐C chemokine receptor type 1 and 2 inhibits flare‐up reactions and neutrophil infiltration. Conclusion: As the first, we show that epidermal CD8+ TRM cells cause ACD flare‐ups by rapid recruitment of neutrophils to the epidermis. [ABSTRACT FROM AUTHOR]

Background: Allergic contact dermatitis (ACD) is classically described as a delayed-type hypersensitivity reaction. However, patients often experience flare-ups characterized by itching erythema, edema, and often vesicles occurring within hours after re-exposure of previously sensitized skin to the specific contact allergen. Recent studies have indicated that skin-resident memory T (T RM ) cells play a central role in ACD. However, the pathogenic role of T RM cells in allergen-induced flare-ups is not known., Methods: By the use of various mouse models and cell depletion protocols, we investigated the role of epidermal T RM cells in flare-up reactions to the experimental contact allergen 1-fluoro-2,4-dinitrobenzene. The inflammatory response was measured by changes in ear thickness, and the cellular composition in epidermis was determined by flow cytometry and confocal microscopy. Finally, adaptive transfer and inhibitors were used to determine the role of T RM cells, neutrophils, and CXCL1/CXCL2 in the response., Results: We show that CD8 + T RM cells initiate massive infiltration of neutrophils in the epidermis within 12 h after re-exposure to the contact allergen. Depletion of neutrophils before re-exposure to the allergen abrogated the flare-up reactions. Furthermore, we demonstrate that CD8 + T RM cells mediate neutrophil recruitment by inducing CXCL1 and CXCL2 production in the skin, and that blockage of the C-X-C chemokine receptor type 1 and 2 inhibits flare-up reactions and neutrophil infiltration., Conclusion: As the first, we show that epidermal CD8 + T RM cells cause ACD flare-ups by rapid recruitment of neutrophils to the epidermis., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)