Toward the Characterization of Human Pro-Resolving Macrophages?

Saas, Philippe; Chagué, Cécile; Maraux, Mélissa; Cherrier, Thomas

doi:10.3389/fimmu.2020.593300

Cited by 18 publications

(19 citation statements)

References 59 publications

(97 reference statements)

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“…Table 1 summarizes the immuno-regulatory functions of SPMs in relation to disease pathology, as discussed here. Interspecies differences in macrophage functions may well exist [discussed in ( 98 )]; however many of the studies on SPMs addressed here, have used human primary macrophages. The importance of lipid mediators in COVID-19 progression is highlighted by studies showing a direct link between a lipidomic imbalance and disease severity.…”

Section: Discussionmentioning

confidence: 99%

Specialized Pro-Resolving Mediators as Potential Regulators of Inflammatory Macrophage Responses in COVID-19

2021

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The recent outbreak of SARS-CoV2 has emerged as one of the biggest pandemics of our century, with outrageous health, social and economic consequences globally. Macrophages may lay in the center of COVID-19 pathogenesis and lethality and treatment of the macrophage-induced cytokine storm has emerged as essential. Specialized pro-resolving mediators (SPMs) hold strong therapeutic potentials in the management of COVID-19 as they can regulate macrophage infiltration and cytokine production but also promote a pro-resolving macrophage phenotype. In this review, we discuss the homeostatic functions of SPMs acting directly on macrophages on various levels, towards the resolution of inflammation. Moreover, we address the molecular events that link the lipid mediators with COVID-19 severity and discuss the clinical potentials of SPMs in COVID-19 immunotherapeutics.

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Section: Discussionmentioning

confidence: 99%

Specialized Pro-Resolving Mediators as Potential Regulators of Inflammatory Macrophage Responses in COVID-19

2021

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“…Other fibroblast functions involved in wound healing are also stimulated in vitro by SuperMApo, including migratory, proliferative and contractive properties. While there is a difference between the biology of mouse and human pro-resolving macrophages ( 47 ), human pro-resolving factors ( i.e ., SuperMApo) also increase the capacity of human fibroblasts isolated from colons of IBD patients to proliferate, migrate and close a wound in vitro . In addition, this targets human fibroblasts either from inflammatory or non-inflammatory intestinal tissues.…”

Section: Discussionmentioning

confidence: 99%

Pro-Resolving Factors Released by Macrophages After Efferocytosis Promote Mucosal Wound Healing in Inflammatory Bowel Disease

et al. 2021

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Nonresolving inflammation is a critical driver of several chronic inflammatory diseases, including inflammatory bowel diseases (IBD). This unresolved inflammation may result from the persistence of an initiating stimulus or from the alteration of the resolution phase of inflammation. Elimination of apoptotic cells by macrophages (a process called efferocytosis) is a critical step in the resolution phase of inflammation. Efferocytosis participates in macrophage reprogramming and favors the release of numerous pro-resolving factors. These pro-resolving factors exert therapeutic effects in experimental autoimmune arthritis. Here, we propose to evaluate the efficacy of pro-resolving factors produced by macrophages after efferocytosis, a secretome called SuperMApo, in two IBD models, namely dextran sodium sulfate (DSS)-induced and T cell transfer-induced colitis. Reintroducing these pro-resolving factors was sufficient to decrease clinical, endoscopic and histological colitis scores in ongoing naive T cell-transfer-induced colitis and in DSS-induced colitis. Mouse primary fibroblasts isolated from the colon demonstrated enhanced healing properties in the presence of SuperMApo, as attested by their increased migratory, proliferative and contractive properties. This was confirmed by the use of human fibroblasts isolated from patients with IBD. Exposure of an intestinal epithelial cell (IEC) line to these pro-resolving factors increased their proliferative properties and IEC acquired the capacity to capture apoptotic cells. The improvement of wound healing properties induced by SuperMApo was confirmed in vivo in a biopsy forceps-wound colonic mucosa model. Further in vivo analysis in naive T cell transfer-induced colitis model demonstrated an improvement of intestinal barrier permeability after administration of SuperMApo, an intestinal cell proliferation and an increase of α-SMA expression by fibroblasts, as well as a reduction of the transcript coding for fibronectin (Fn1). Finally, we identified TGF-β, IGF-I and VEGF among SuperMApo as necessary to favor mucosal healing and confirmed their role both in vitro (using neutralizing antibodies) and in vivo by depleting these factors from efferocytic macrophage secretome using antibody-coated microbeads. These growth factors only explained some of the beneficial effects induced by factors released by efferocytic macrophages. Overall, the administration of pro-resolving factors released by efferocytic macrophages limits intestinal inflammation and enhance tissue repair, which represents an innovative treatment of IBD.

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“…Their main biological activity is to inhibit the synthesis of adhesion molecules in endothelial and epithelial cells. They lower the generation of IL-6, IL-8, and monocyte chemoattractant protein-1, dampen the production of reactive oxygen species, and drive towards an anti-inflammatory M2 phenotype [93]. The level of pro-resolving lipid mediators Lipoxin A4, Resolvin E1, and Resolvin D1 was significantly lower in active RA when compared to healthy or in remission individuals [94].…”

Section: Lipid Mediators Of Inflammation Resolutionmentioning

confidence: 98%

The Effect of Acknowledged and Novel Anti-Rheumatic Therapies on Periodontal Tissues—A Narrative Review

et al. 2021

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Rheumatoid arthritis (RA) and periodontal disease (PD) are chronic complex inflammatory diseases with several common susceptibility factors, especially genetic and environmental risk factors. Although both disorders involve a perturbation of the immune–inflammatory response at multiple levels, one major difference between the two is the different locations in which they develop. RA is triggered by an exaggerated autoimmune response that targets joints, while periodontal disease occurs as a consequence of the subgingival periodontopathogenic microbiota. Current treatment models in both pathologies involve the stratification of patients to allow therapeutic individualization according to disease stage, complexity, progression, lifestyle, risk factors, and additional systemic diseases. Therapeutic guidelines for RA comprise of five main classes of drugs: non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, glucocorticoids, and disease-modifying anti-rheumatic drugs (DMARDs): biologic and non-biologic. Although various treatment options are available, a definitive treatment remains elusive, therefore research is ongoing in this area. Several alternatives are currently being tested, such as matrix metalloproteinases (MMP) inhibitors, toll-like receptors (TLR) blockers, pro-resolution mediators, anti-hypoxia inducing factors, stem cell therapy, NLRP3 inhibitors and even natural derived compounds. Although the link between PD and rheumatoid arthritis has been investigated by multiple microbiology and immunology studies, the precise influence and causality is still debated in the literature. Furthermore, the immunomodulatory effect of anti-rheumatic drugs on the periodontium is still largely unknown. In this narrative review, we explore the mechanisms of interaction and the potential influence that anti-rheumatoid medication, including novel treatment options, has on periodontal tissues and whether periodontal health status and treatment can improve the prognosis of an RA patient.

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Toward the Characterization of Human Pro-Resolving Macrophages?

Cited by 18 publications

References 59 publications

Specialized Pro-Resolving Mediators as Potential Regulators of Inflammatory Macrophage Responses in COVID-19

Specialized Pro-Resolving Mediators as Potential Regulators of Inflammatory Macrophage Responses in COVID-19

Pro-Resolving Factors Released by Macrophages After Efferocytosis Promote Mucosal Wound Healing in Inflammatory Bowel Disease

The Effect of Acknowledged and Novel Anti-Rheumatic Therapies on Periodontal Tissues—A Narrative Review

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