Dendritic cell derived exosomes loaded with immunoregulatory cargo reprogram local immune responses and inhibit degenerative bone disease in vivo
Open accessAbstract
Chronic bone degenerative diseases represent a major threat to the health and well‐being of the population, particularly those with advanced age. This study isolated exosomes (EXO), natural nano‐particles, from dendritic cells, the “directors” of the immune response, to examine the immunobiology of DC EXO in mice, and their ability to reprogram immune cells responsible for experimental alveolar bone loss in vivo . Distinct DC EXO subtypes including immune‐regulatory (regDC EXO), loaded with TGFB1 and IL10 after purification, along with immune stimulatory (stimDC EXO) and immune “null” immature (iDCs EXO) unmodified after purification, were delivered via I.V. route or locally into the soft tissues overlying the alveolar bone. Locally administrated regDC EXO showed high affinity for inflamed sites, and were taken up by both DCs and T cells in situ . RegDC EXO‐encapsulated immunoregulatory cargo (TGFB1 and IL10) was protected from proteolytic degradation. Moreover, maturation of recipient DCs and induction of Th17 effectors was suppressed by regDC EXO, while T‐regulatory cell recruitment was promoted, resulting in inhibition of bone resorptive cytokines and reduction in osteoclastic bone loss. This work is the first demonstration of DC exosome‐based therapy for a degenerative alveolar bone disease and provides the basis for a novel treatment strategy.
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Pg-induced exosomes of the senescence-associated secretory phenotype express integrins and lectins that promote cell binding at the inflamed site.
“Pg-induced EXO of the SASP express integrins and lectins that promote cell binding at the inflamed site [19,20].”
From Oral Microbially-Induced Small Extracellular Vesicles Cross the Blood–Brain Barrier (2024) · cites this paper as [20]
The Discussion states that dendritic-cell-derived exosomes express integrins and lectins that could promote binding and persistence at an inflamed site. It does not establish that these exosomes were Pg-induced or part of the senescence-associated secretory phenotype; those qualifiers are not supported by this paper. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPg-induced exosomes are enriched with virulence factors from Pg including gingipains, enabling them to disrupt barrier functions of the epithelium and penetrate through interstitial spaces and lymphatics to enter systemic circulation.
“Moreover, those EXO are enriched with virulence factors from Pg including gingipains, a potent proteolytic enzyme, enabling them to disrupt barrier functions of the epithelium and penetrate through interstitial spaces and lymphatics to find their way into systemic circulation.”
From Oral Microbially-Induced Small Extracellular Vesicles Cross the Blood–Brain Barrier (2024) · cites this paper as [20]
The Discussion describes immunoregulatory dendritic-cell exosomes persisting at the gingival disease site, while the Methods describe a periodontitis model dependent on endogenous flora. Searches for Pg-induced exosomes, gingipains, epithelial barrier disruption, lymphatic passage, and systemic circulation found no passage addressing the attributed claim. (LLM, conf=0.75)
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- Authors
- Elashiry, M., Elashiry, M. M., Elsayed, R., Rajendran, M., Auersvald, C., Zeitoun, R., Rashid, M. H., Ara, R., Meghil, M. M., Liu, Y., Arbab, A. S., Arce, R. M., Hamrick, M., Elsalanty, M., Brendan, M., Pacholczyk, R., & Cutler, C. W.
- Affiliations
- Ain Shams University (EG)
- Augusta University (US)
- Department of Periodontics Dental College of Georgia at Augusta University GA USA
- The University of Texas Health Science Center at Houston (US)
- Western University of Health Sciences (US)
- Department of Cellular Biology and Anatomy Medical College of Georgia at Augusta University GA USA
- Georgia Cancer Center Augusta GA USA
- Corresponding author
- Cutler, Christopher W.
- ORCID
- Venue
- Journal of Extracellular Vesicles
- Publisher
- Wiley
- Published
- 2020-08-07
- Volume
- 9
- Issue
- 1
- Pages
- 1795362-1795362
- ISSN
- 2001-3078 (ISSN-L)
- PMC
- PMC7480413
- OpenAlex
- W3048286913
- Cited by
- 116
- References
- 76
- Citations by year
- 2026: 13 · 2025: 25 · 2024: 21 · 2023: 16 · 2022: 20 · 2021: 19 · 2020: 2
- FWCI
- 4.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Extracellular Vesicles (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Carlos and Marguerite Mason Trust (1)
- NIH-NIDCR (R01 DE014328)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- exosome therapy, alveolar bone loss, TGF-β1, IL-10, Th17 cells, regulatory T cells, osteoclasts, bone resorption, extracellular vesicles, local delivery, dendritic cell maturation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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