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Untangling Local Pro-Inflammatory, Reparative, and Regulatory Damage-Associated Molecular-Patterns (DAMPs) Pathways to Improve Transplant Outcomes.
- Source :
-
Frontiers in immunology [Front Immunol] 2021 Feb 23; Vol. 12, pp. 611910. Date of Electronic Publication: 2021 Feb 23 (Print Publication: 2021). - Publication Year :
- 2021
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Abstract
- Detrimental inflammatory responses after solid organ transplantation are initiated when immune cells sense pathogen-associated molecular patterns (PAMPs) and certain damage-associated molecular patterns (DAMPs) released or exposed during transplant-associated processes, such as ischemia/reperfusion injury (IRI), surgical trauma, and recipient conditioning. These inflammatory responses initiate and propagate anti-alloantigen (AlloAg) responses and targeting DAMPs and PAMPs, or the signaling cascades they activate, reduce alloimmunity, and contribute to improved outcomes after allogeneic solid organ transplantation in experimental studies. However, DAMPs have also been implicated in initiating essential anti-inflammatory and reparative functions of specific immune cells, particularly Treg and macrophages. Interestingly, DAMP signaling is also involved in local and systemic homeostasis. Herein, we describe the emerging literature defining how poor outcomes after transplantation may result, not from just an over-abundance of DAMP-driven inflammation, but instead an inadequate presence of a subset of DAMPs or related molecules needed to repair tissue successfully or re-establish tissue homeostasis. Adverse outcomes may also arise when these homeostatic or reparative signals become dysregulated or hijacked by alloreactive immune cells in transplant niches. A complete understanding of the critical pathways controlling tissue repair and homeostasis, and how alloimmune responses or transplant-related processes disrupt these will lead to new immunotherapeutics that can prevent or reverse the tissue pathology leading to lost grafts due to chronic rejection.<br />Competing Interests: HT is a listed inventor on patent application PCT/US2019/030547 (“MATRIX BOUND VESICLES (MBVS) CONTAINING IL-33 AND THEIR USE”). The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2021 Dwyer and Turnquist.)
- Subjects :
- Alarmins genetics
Biomarkers
Fibrosis
Gene Expression Regulation
Humans
Immunity
Immunomodulation
Inflammation pathology
Inflammation Mediators
Macrophages immunology
Macrophages metabolism
Reperfusion Injury etiology
Reperfusion Injury metabolism
Reperfusion Injury pathology
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory metabolism
Transplantation, Homologous
Treatment Outcome
Alarmins metabolism
Inflammation etiology
Inflammation metabolism
Organ Transplantation adverse effects
Organ Transplantation methods
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33708206
- Full Text :
- https://doi.org/10.3389/fimmu.2021.611910