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Local delivery strategies to restore immune homeostasis in the context of inflammation.

ABSTRACT: Immune homeostasis is maintained by a precise balance between effector immune cells and regulatory immune cells. Chronic deviations from immune homeostasis, driven by a greater ratio of effector to regulatory cues, can promote the development and propagation of inflammatory diseases/conditions (i.e., autoimmune diseases, transplant rejection, etc.). Current methods to treat chronic inflammation rely upon systemic administration of non-specific small molecules, resulting in broad immunosuppression with unwanted side effects. Consequently, recent studies have developed more localized and specific immunomodulatory approaches to treat inflammation through the use of local biomaterial-based delivery systems. In particular, this review focuses on (1) local biomaterial-based delivery systems, (2) common materials used for polymeric-delivery systems and (3) emerging immunomodulatory trends used to treat inflammation with increased specificity.

SUBMITTER: Bentley ER

PROVIDER: S-EPMC8556365 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Local delivery strategies to restore immune homeostasis in the context of inflammation.

Bentley Elizabeth R ER Little Steven R SR

Advanced drug delivery reviews 20210913

Immune homeostasis is maintained by a precise balance between effector immune cells and regulatory immune cells. Chronic deviations from immune homeostasis, driven by a greater ratio of effector to regulatory cues, can promote the development and propagation of inflammatory diseases/conditions (i.e., autoimmune diseases, transplant rejection, etc.). Current methods to treat chronic inflammation rely upon systemic administration of non-specific small molecules, resulting in broad immunosuppressio ...[more]

PMID: 34530013

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Project description:Many chronic inflammatory diseases are attributed to disturbances in host-microbe interactions, which drive immune-mediated tissue damage. Depending on the anatomic setting, a chronic inflammatory disease can exert unique local and systemic influences, which provide an exceptional opportunity for understanding disease mechanism and testing therapeutic interventions. The oral cavity is an easily accessible environment that allows for protective interventions aiming at modulating the immune response to control disease processes driven by a breakdown of host-microbe homeostasis. Periodontal disease (PD) is a prevalent condition in which quantitative and qualitative changes of the oral microbiota (dysbiosis) trigger nonresolving chronic inflammation, progressive bone loss, and ultimately tooth loss. Here, we demonstrate the therapeutic benefit of local sustained delivery of the myeloid-recruiting chemokine (C-C motif) ligand 2 (CCL2) in murine ligature-induced PD using clinically relevant models as a preventive, interventional, or reparative therapy. Local delivery of CCL2 into the periodontium inhibited bone loss and accelerated bone gain that could be ascribed to reduced osteoclasts numbers. CCL2 treatment up-regulated M2-macrophage and downregulated proinflammatory and pro-osteoclastic markers. Furthermore, single-cell ribonucleic acid (RNA) sequencing indicated that CCL2 therapy reversed disease-associated transcriptomic profiles of murine gingival macrophages via inhibiting the triggering receptor expressed on myeloid cells-1 (TREM-1) signaling in classically activated macrophages and inducing protein kinase A (PKA) signaling in infiltrating macrophages. Finally, 16S ribosomal ribonucleic acid (rRNA) sequencing showed mitigation of microbial dysbiosis in the periodontium that correlated with a reduction in microbial load in CCL2-treated mice. This study reveals a novel protective effect of CCL2 local delivery in PD as a model for chronic inflammatory diseases caused by a disturbance in host-microbe homeostasis.

Dataset Information

Local delivery strategies to restore immune homeostasis in the context of inflammation.

Publications

Local delivery strategies to restore immune homeostasis in the context of inflammation.

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