The Mannose Receptor: From Endocytic Receptor and Biomarker to Regulator of (Meta)Inflammation

Zande, Hendrik J. P. van der; Nitsche, Dominik; Schlautmann, Laura; Guigas, Bruno; Burgdorf, Sven

doi:10.3389/fimmu.2021.765034

Cited by 88 publications

(69 citation statements)

References 132 publications

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“…As predicted by the non-inflammatory environment, the IGF1R lo CD14 + cells produced higher levels of IL10 and IL1β as judged by RNA-seq and by protein cytokine levels in cell culture supernatants ( Figures 4C, D ), a sign of M2-type macrophages. In addition to cytokines, IGF1R lo CD14 + cells expressed higher levels of MHCII receptors HLA-DQA1, HLA-DPA1 and HLA-DRB1, and in C-type lectin binding receptors including the macrophage scavenger receptor 1 (MSR1) and the mannose receptor 1 (MRC1) directly interacting with T cells ( 47 ) ( Figure 4D ), and CLEC6A/DCIR2, CLEC4E/MINCLE, CLEC5A/MDL1, CLEC12A/MICL, CLEC4A/DCIR ( Figure 4E ) essential for immunoregulation of T and B cell function ( 48 – 51 ).…”

Section: Resultsmentioning

confidence: 99%

“…The molecular nature of the direct interaction between MHCII + APC and B cells has not been elucidated in depth and requires further studies. The C-type lectins upregulated in IGF1R lo CD14 + cells of RA patients and in APC after IGF1R inhibition in mice and their emerging immune regulatory function ( 47 , 50 , 51 ) are the candidate mediators of such an interaction.…”

Section: Discussionmentioning

confidence: 99%

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IGF1R signalling is a guardian of self-tolerance restricting autoantibody production

Erlandsson

Erdogan²,

Wasén³

et al. 2022

Front. Immunol.

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ObjectiveInsulin-like growth factor 1 receptor (IGF1R) acts at the crossroad between immunity and cancer, being an attractive therapeutic target in these areas. IGF1R is broadly expressed by antigen-presenting cells (APC). Using mice immunised with the methylated albumin from bovine serum (BSA-immunised mice) and human CD14+ APCs, we investigated the role that IGF1R plays during adaptive immune responses.MethodsThe mBSA-immunised mice were treated with synthetic inhibitor NT157 or short hairpin RNA to inhibit IGF1R signalling, and spleens were analysed by immunohistology and flow cytometry. The levels of autoantibody and cytokine production were measured by microarray or conventional ELISA. The transcriptional profile of CD14+ cells from blood of 55 patients with rheumatoid arthritis (RA) was analysed with RNA-sequencing.ResultsInhibition of IGF1R resulted in perifollicular infiltration of functionally compromised S256-phosphorylated FoxO1+ APCs, and an increased frequency of IgM+CD21+ B cells, which enlarged the marginal zone (MZ). Enlargement of MHCII+CD11b+ APCs ensured favourable conditions for their communication with IgM+ B cells in the MZ. The reduced expression of ICOSL and CXCR5 by APCs after IGF1R inhibition led to impaired T cell control, which resulted in autoreactivity of extra-follicular B cells and autoantibody production. In the clinical setting, the low expression of IGF1R on CD14+ APCs was associated with an involuted FOXO pathway, non-inflammatory cell metabolism and a high IL10 production characteristic for tolerogenic macrophages. Furthermore, autoantibody positivity was associated with low IGF1R signalling in CD14+ APCs.ConclusionsIn experimental model and in patient material, this study demonstrates that IGF1R plays an important role in preventing autoimmunity. The study raises awareness of that immune tolerance may be broken during therapeutic IGF1R targeting.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

IGF1R signalling is a guardian of self-tolerance restricting autoantibody production

Erlandsson

Erdogan²,

Wasén³

et al. 2022

Front. Immunol.

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“…A third strategy relies on the glucose-dependent clearance of insulin analogues via immune cells, which is not frequently used compared to the strategies mentioned above. Kupffer cells in the liver express mannose receptor (MR) C-type 1 that can recognize the mannose moiety on other molecules . Thus, the incorporation of mannose onto insulin molecules can enable insulin to bind to MR C-type 1, therefore accelerating insulin’s clearance rate from the blood and controlling its blood concentration.…”

Section: Glucose-responsive Mechanisms and Associated Materials Designmentioning

confidence: 99%

Materials and Carriers Development for Glucose-Responsive Insulin

Yao

Wang

et al. 2022

Acc. Mater. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: Insulin replacement therapy is an essential and effective treatment strategy for controlling the blood glucose level (BGL) of people without sufficient endogenous insulin production. However, insulin therapy faces challenges such as daily multiple injections and hypoglycemia risk arising from its narrow therapeutic index, which together leads to poor BGL control. Thus, glucose-responsive insulin delivery systems that can mimic β-cell function are developed to improve BGL control and reduce injection frequency. Glucose-responsive materials-based insulin delivery systems are competent in tightly controlling the BGL with an additional benefit of reducing the hypoglycemia risk. Glucose-responsive materials generally work together with three major glucose-sensing elements: glucose oxidase (GOx), phenylboronic acid (PBA), and glucose-binding molecules. Based on glucose-sensing elements, glucose-responsive materials are rationally designed to sense the change in glucose concentration or indirect signals associated with glucose fluctuation, such as pH, H 2 O 2 concentration, and O 2 level, and adjust their physical or chemical characteristics accordingly.Many advanced glucose-responsive materials have been developed along this line, aiming to achieve robust glucose-responsive insulin release performance and elevate their therapeutic outcome. These advanced materials mainly include organic materials such as biomacromolecules, synthetic polymers, polypeptides, liposomes, and inorganic materials such as calcium phosphate (Ca 3 (PO 4 ) 2 ) and metal organic frameworks (MOFs). Built on these glucose-responsive materials, other groups and we have developed various carriers such as hydrogels, micro/nanoparticles, liposomes, complexes, cell−drug conjugates, and microneedle (MN) array patches. These delivery systems can release insulin via glucose-stimulated swelling/contraction, dissolution, pore size change, charge reversal, and polymer deterioration. Also, these carriers are continuously under development to accelerate responsive rate, increase response index, and improve biocompatibility. Our group focuses on the synthesis of glucoseresponsive materials and the design of glucose-responsive MN array patches, hydrogels, insulin complexes, and cell−drug conjugates for the treatment of diabetes in a dose-, spatial-, and temporal-controlled fashion. These closed-loop insulin delivery systems can respond to BGL alternation and secrete the correct amount of insulin accordingly. Also, MN array patches have the additional merits of reducing pain and easy administration.In this Account, we briefly introduce the glucose-responsive mechanisms and the relevant requirements of materials that can work cooperatively with these mechanisms. Then, we highlight our group's work in preparing various materials for constructing glucoseresponsive carriers. We are mainly aiming to improve glucose-responsive properties, administration feasibility, and in vivo biocompatibility. The challenges and perspe...

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“… 23 , 31 CD206, also termed mannose receptor (MR), has been reported to be correlated with inflammatory diseases and induce macrophage activation. 32 Therefore, it is necessary to reprogram macrophages toward the M2 phenotype at appropriate time points in anti-infection therapy. Some scholars have found that nanoparticles with cell membrane modified on their surface can reduce their clearance by the immune system and ensure sufficient doses of nanoparticles to reach the target tissue.…”

Section: Introductionmentioning

confidence: 99%

Multi-Modal Imaging Monitored M2 Macrophage Targeting Sono-Responsive Nanoparticles to Combat MRSA Deep Infections

Chen¹,

Wang²,

Tang³

et al. 2022

IJN

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Background: MRSA with high morbidity and mortality is prone to cause serious infection, SDT has become a new antibiotic-free modality for bacterial infection treatment. Switching from proinflammatory M1 macrophages to anti-inflammatory M2 macrophages dominant could activate the immune system to generate an anti-infection immune response. Methods: Herein, we developed M2 macrophages derived cell membranes coated PLGA nanoparticles with IR780 encapsulation (M2/IR780@PLGA) for antibacterial SDT and subsequent M2 macrophage polarization to enhance the therapeutic efficacy of MRSA myositis. For in situ visualization of antibacterial SDT, both diagnostic high-frequency US and magnetic resonance imaging (MRI) were introduced to monitor the sono-therapeutic progression of M2/IR780@PLGA nanoparticles in mice with bacterial myositis. Results: Our developed M2/IR780@PLGA nanoparticles exhibited excellent antibacterial effects due to the IR780 under lowfrequency US irradiation in vitro. In an MRSA-infected mice model, a great deal of M2/IR780@PLGA nanoparticles accumulated at the site of inflammation due to M2 macrophage coating. The infected legs in the M2/IR780@PLGA nanoparticles-based SDT group were significantly smaller, fewer blood flow signals, a slight muscular edema without obvious intermuscular abscesses under highfrequency US and MR images guidance. Histopathology proved the infected legs in the M2/IR780@PLGA nanoparticles-mediated SDT group had less clumped bacteria infiltration, more M2 macrophage expression and less M1 macrophage expression. The percentage of mature dendritic cells in spleens was much higher in the group of mice with M2/IR780@PLGA nanoparticles-based SDT. Conclusion:This study provides a promising nanoparticles-based SDT anti-bacterial strategy, which could effectively enhance the antibacterial SDT and subsequent promote M2 macrophage polarization to boost the therapeutic efficacy of MRSA myositis.

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The Mannose Receptor: From Endocytic Receptor and Biomarker to Regulator of (Meta)Inflammation

Cited by 88 publications

References 132 publications

IGF1R signalling is a guardian of self-tolerance restricting autoantibody production

IGF1R signalling is a guardian of self-tolerance restricting autoantibody production

Materials and Carriers Development for Glucose-Responsive Insulin

Multi-Modal Imaging Monitored M2 Macrophage Targeting Sono-Responsive Nanoparticles to Combat MRSA Deep Infections

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