Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB), a skin fragility disorder that, unexpectedly, manifests also with elevated colonization of commensal bacteria and frequent wound infections. Here, we describe an unprecedented systemic function of collagen VII as a member of a unique innate immune-supporting multiprotein complex in spleen and lymph nodes. In this complex, collagen VII specifically binds and sequesters the innate immune activator cochlin in the lumen of lymphoid conduits. In genetic mouse models, loss of collagen VII increased bacterial colonization by diminishing levels of circulating cochlin LCCL domain. Intraperitoneal injection of collagen VII, which restored cochlin in the spleen, but not in the skin, reactivated peripheral innate immune cells via cochlin and reduced bacterial skin colonization. Systemic administration of the cochlin LCCL domain was alone sufficient to diminish bacterial supercolonization of RDEB mouse skin. Human validation demonstrated that RDEB patients displayed lower levels of systemic cochlin LCCL domain with subsequently impaired macrophage response in infected wounds. This study identifies an intrinsic innate immune dysfunction in RDEB and uncovers a unique role of the lymphoid extracellular matrix in systemic defense against bacteria.collagen VII | innate immunity | bacteria | recessive dystrophic epidermolysis bullosa | cochlin
Discussion | The results of this study reveal important differences in the microbiota of HS lesions in obese vs nonobese patients. Gut flora alterations are seen in obese patients, 4,5 and HS has been associated with obesity. It is possible that altered gut or skin flora could have a pathogenic role in HS. Some of the limitations of the present study include the use of retrospective data and the lack of a control group consisting of patients with no history of HS. Although these cultures were obtained from purulence extruding from HS lesions, the bacterial culture results could represent skin or gut flora contamination. Information about the specific anatomic locations of HS cultures was not available. Because only the first recorded culture of each patient was analyzed, it is unknown if the culture results would change with time and further antibiotic therapy. The use of data obtained from swabbased cultures may also represent a potential limitation because DNA-based approaches to microbial analysis may yield more information and lead to identification of organisms that are not cultivable. The use of more advanced microbiome techniques may be an important consideration for future studies. These data indicate that further research is needed to elucidate the role of specific bacterial species in the pathogenesis of HS and may suggest a role for targeted treatment of specific bacterial species in this disorder.
A 62-year-old woman with sarcoidosis II, status post systemic steroid treatment, developed an inflammatory, infiltrative skin lesion in the area of a traumatic haematoma of the right forearm. The clinical appearance at first corresponded to bullous erysipelas. Antibiotic therapy, which was instituted immediately, proved to be ineffective. A microbiological swab revealed infection with Cryptococcus neoformans. A systemic cryptococcosis could be excluded. Therapy with 200 mg itraconazole twice daily resulted in a prompt improvement.
Mid-dermal elastolysis is a rare peculiar entity clinically characterized by fine wrinkles and perifollicular protrusions that give the skin an aged or peau d'orange appearance. The histopathologic correlate is a bandlike loss of elastic tissue within the mid-dermis.We present a typical case with prominent perifollicular protrusions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.