PMID- 31925827 OWN - NLM STAT- MEDLINE DCOM- 20210812 LR - 20210812 IS - 1365-2222 (Electronic) IS - 0954-7894 (Linking) VI - 50 IP - 5 DP - 2020 May TI - Neuronal branching of sensory neurons is associated with BDNF-positive eosinophils in atopic dermatitis. PG - 577-584 LID - 10.1111/cea.13560 [doi] AB - BACKGROUND: Pruritus is a major symptom of atopic dermatitis (AD) and is transmitted by a subpopulation of non-myelinated C-type free nerve endings in the epidermis and upper dermis. Stimulation of these nerve terminals is affected by histamine, neurotrophins and physical factors. Eosinophils of patients with AD are a source of neurotrophins, including brain-derived neurotrophic factor (BDNF), levels of which correlate with disease severity. OBJECTIVE: The purpose of this study was to determine the anatomical localization of eosinophils in the skin of patients with AD with regard to peripheral nerves and to investigate whether eosinophils induce sprouting and neurite outgrowth in murine sensory neurons. METHODS: Cryosections of skin derived from AD and control (NA) patients were subjected to immunofluorescence analysis with markers for eosinophils, BDNF and neuronal cells. Stimulated eosinophil supernatants were used for the treatment of cultured peripheral mouse dorsal root ganglia (DRG) neurons followed by morphometric analysis. RESULTS: Dermal axon density and the proximity of eosinophils to nerve fibres were significantly higher in AD patients vs NA. Both neuronal projections and eosinophils expressed BDNF. Furthermore, activated eosinophil supernatants induced BDNF-dependent mouse DRG neuron branching. CONCLUSIONS AND CLINICAL RELEVANCE: Our results indicate that BDNF-positive eosinophils are also localized in close proximity with nerve fibres in AD, suggesting a functional relationship between BDNF-expressing eosinophils and neuronal projections. These observations suggest that eosinophils may have considerable impact on pruritus by supporting sensory nerve branching. CI - (c) 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd. FAU - Guseva, Daria AU - Guseva D AD - Department of Cellular Neurophysiology, Hannover Medical School, Hannover, Germany. AD - Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany. FAU - Rudrich, Urda AU - Rudrich U AD - Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany. FAU - Kotnik, Nika AU - Kotnik N AD - Division of Experimental Allergology and Immunodermatology, University of Oldenburg, Oldenburg, Germany. FAU - Gehring, Manuela AU - Gehring M AD - Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany. FAU - Patsinakidis, Nikolaos AU - Patsinakidis N AD - University Clinic of Dermatology and Allergy, University of Oldenburg, Oldenburg, Germany. FAU - Agelopoulos, Konstantin AU - Agelopoulos K AD - Department of Dermatology and Center for Chronic Pruritus, University Hospital Munster, Munster, Germany. FAU - Stander, Sonja AU - Stander S AD - Department of Dermatology and Center for Chronic Pruritus, University Hospital Munster, Munster, Germany. FAU - Homey, Bernhard AU - Homey B AD - Department of Dermatology, Heinrich-Heine-University, Dusseldorf, Germany. FAU - Kapp, Alexander AU - Kapp A AD - Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany. FAU - Gibbs, Bernhard F AU - Gibbs BF AUID- ORCID: 0000-0002-0537-228X AD - Division of Experimental Allergology and Immunodermatology, University of Oldenburg, Oldenburg, Germany. FAU - Ponimaskin, Evgeni AU - Ponimaskin E AD - Department of Cellular Neurophysiology, Hannover Medical School, Hannover, Germany. AD - Institute of Cytology and Genetics, Novosibirsk, Russia. FAU - Raap, Ulrike AU - Raap U AUID- ORCID: 0000-0002-9573-4714 AD - Division of Experimental Allergology and Immunodermatology, University of Oldenburg, Oldenburg, Germany. AD - University Clinic of Dermatology and Allergy, University of Oldenburg, Oldenburg, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200204 PL - England TA - Clin Exp Allergy JT - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JID - 8906443 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 7171WSG8A2 (BDNF protein, human) SB - IM MH - Adolescent MH - Adult MH - Brain-Derived Neurotrophic Factor/*immunology MH - *Dermatitis, Atopic/immunology/pathology MH - *Dermis/immunology/innervation/pathology MH - *Eosinophils/immunology/pathology MH - *Epidermis/immunology/innervation/pathology MH - Female MH - Humans MH - Male MH - *Sensory Receptor Cells/immunology/pathology OTO - NOTNLM OT - BDNF OT - DRG neurons OT - atopic dermatitis OT - eosinophils EDAT- 2020/01/12 06:00 MHDA- 2021/08/13 06:00 CRDT- 2020/01/12 06:00 PHST- 2019/04/30 00:00 [received] PHST- 2019/12/20 00:00 [revised] PHST- 2020/01/03 00:00 [accepted] PHST- 2020/01/12 06:00 [pubmed] PHST- 2021/08/13 06:00 [medline] PHST- 2020/01/12 06:00 [entrez] AID - 10.1111/cea.13560 [doi] PST - ppublish SO - Clin Exp Allergy. 2020 May;50(5):577-584. doi: 10.1111/cea.13560. Epub 2020 Feb 4.