Visualization of autoantibodies and neutrophils in vivo identifies novel checkpoints in autoantibody-induced tissue injury
| Autor: | Ralf Ludwig, Peter König, Mario Pieper, Katja Bieber, Rebecca Pfündl, Detlef Zillikens, Jennifer E. Hundt, Hiroaki Iwata |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Epidermolysis bullosa acquisita Pemphigoid Collagen Type VII Neutrophils Biopsy Fluorescent Antibody Technique lcsh:Medicine Autoimmunity Inflammation Article Autoimmune Diseases Green fluorescent protein Mice 03 medical and health sciences 0302 clinical medicine In vivo medicine Animals lcsh:Science Autoantibodies Skin Multidisciplinary medicine.diagnostic_test Chemistry lcsh:R Autoantibody medicine.disease Extravasation Experimental models of disease Disease Models Animal 030104 developmental biology Immunoglobulin G 030220 oncology & carcinogenesis Immunology lcsh:Q Disease Susceptibility medicine.symptom Biomarkers |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-60233-w |
| Popis: | In several autoimmune diseases, e.g., pemphigoid disease (PD), autoantibodies are the direct cause of pathology. Albeit key requirements for antibody-mediated diseases were identified, their interactions and exact temporal and spatial interactions remained elusive. The skin is easily accessible for imaging. Thus, we selected epidermolysis bullosa acquisita (EBA), a PD with autoantibodies to type VII collagen (COL7), to visualize interactions of autoantibodies, target tissue and effector cells (neutrophils). Following injection into mice, anti-COL7 IgG bound to the dermal-epidermal junction (DEJ) within minutes. We unexpectedly observed an inhomogeneous distribution of autoantibodies along the DEJ. Thus, we hypothesized that specific external triggers may affect autoantibody distribution. Indeed, mechanical irritation led to an increased autoantibody binding along the DEJ. Subsequently, anti-COL7 IgG was injected into mice expressing green fluorescent protein under the LysM promoter (LysM-eGFP) mice. This allows to visualize myeloid cells in vivo in these animals. Using multiphoton imaging, we observed a limited extravasation of LysM-eGFP+ cells into skin was observed within 24 hours. Intriguingly, LysM-eGFP+ cells did not immediately co-localize with autoantibodies, which was only noted at later time points. Of note, interactions of LysM-eGFP+ with the autoantibodies at the DEJ were short-lived. Collectively, our results define the following checkpoints for autoantibody-induced tissue injury: (i) autoantibody egress to target tissue influenced by mechanical trigger factors, (ii) neutrophil recruitment into the vicinity of autoantibody deposits and (iii) short-term neutrophil localization to these deposits, as well as (iv) delayed recruitment of neutrophils with subsequent autoantibody-induced inflammation. |
| Databáze: | OpenAIRE |
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