TY - JOUR
T1 - Dendritic cell derived exosomes loaded with immunoregulatory cargo reprogram local immune responses and inhibit degenerative bone disease in vivo
AU - Elashiry, Mahmoud
AU - Elashiry, Mohamed M.
AU - Elsayed, Ranya
AU - Rajendran, Mythily
AU - Auersvald, Carol
AU - Zeitoun, Rana
AU - Rashid, Mohammad H.
AU - Ara, Roxan
AU - Meghil, Mohamed M.
AU - Liu, Yutao
AU - Arbab, Ali S.
AU - Arce Munoz, Roger Mauricio
AU - Hamrick, Mark
AU - Elsalanty, Mohammed Elsayed
AU - Brendan, Marshall
AU - Pacholczyk, Rafal
AU - Cutler, Christopher W.
N1 - Publisher Copyright:
© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - (MeSH): Dendritic Cells
KW - alveolar Bone loss
KW - exosomes
KW - inflammation
KW - periodontitis
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U2 - 10.1080/20013078.2020.1795362
DO - 10.1080/20013078.2020.1795362
M3 - Article
AN - SCOPUS:85089141442
SN - 2001-3078
VL - 9
JO - Journal of Extracellular Vesicles
JF - Journal of Extracellular Vesicles
IS - 1
M1 - 1795362
ER -