CD64: An Attractive Immunotherapeutic Target for M1-type Macrophage Mediated Chronic Inflammatory Diseases

Akinrinmade, Olusiji A.; Chetty, Shivan; Daramola, Adebukola K.; Islam, Mukit-ul; Thepen, Theo; Barth, Stefan

doi:10.3390/biomedicines5030056

Cited by 74 publications

(62 citation statements)

References 92 publications

(113 reference statements)

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“…N.D. Not determined. macrophages (10)(11)(12). The TLR2 and TLR4 pattern recognition marker receptors are more highly expressed on BMDMs (Figure 3B and p value list).…”

Section: M1 Markersmentioning

confidence: 94%

Bone Marrow-Derived and Elicited Peritoneal Macrophages Are Not Created Equal: The Questions Asked Dictate the Cell Type Used

et al. 2020

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Macrophages are a heterogeneous and plastic population of cells whose phenotype changes in response to their environment. Macrophage biologists utilize peritoneal (pMAC) and bone marrow-derived macrophages (BMDM) for in vitro studies. Given that pMACs mature in vivo while BMDM are ex vivo differentiated from stem cells, it is likely that their responses differ under experimental conditions. Surprisingly little is known about how BMDM and pMACs responses compare under the same experimental conditionals. While morphologically similar with respect to forward and side scatter by flow cytometry, reports in the literature suggest that pMACs are more mature than their BMDM counterparts. Given the dearth of information comparing BMDM and pMACs, this work was undertaken to test the hypothesis that elicited pMACs are more responsive to defined conditions, including phagocytosis, respiratory burst, polarization, and cytokine and chemokine release. In all cases, our hypothesis was disproved. At steady state, BMDM are more phagocytic (both rate and extent) than elicited pMACs. In response to polarization, they upregulate chemokine and cytokine gene expression and release more cytokines. The results demonstrate that BMDM are generally more responsive and poised to respond to their environment, while pMAC responses are, in comparison, less pronounced. BMDM responses are a function of intrinsic differences, while pMAC responses reflect their differentiation in the context of the whole animal. This distinction may be important in knockout animals, where the pMAC phenotype may be influenced by the absence of the gene of interest.

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“…N.D. Not determined. macrophages (10)(11)(12). The TLR2 and TLR4 pattern recognition marker receptors are more highly expressed on BMDMs (Figure 3B and p value list).…”

Section: M1 Markersmentioning

confidence: 94%

Bone Marrow-Derived and Elicited Peritoneal Macrophages Are Not Created Equal: The Questions Asked Dictate the Cell Type Used

et al. 2020

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“…Currently, there are new and interesting strategies to change the M1/M2 ratio using different agents. For example, Fc γ RI receptor (CD64), which is up‐regulated in macrophages from chronic inflammation sites was recently targeted with monoclonal antibodies, demonstrating a clinical potential . Taking into account the importance of a correctly balanced M1/M2 ratio in cancer and several autoimmune diseases, new therapies seek to selectively mark and deplete specific macrophage subpopulations.…”

Section: Future Perspectivesmentioning

confidence: 99%

Implications of macrophage polarization in autoimmunity

et al. 2018

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SummaryMacrophages are extremely heterogeneous and plastic cells with an important role not only in physiological conditions, but also during inflammation (both for initiation and resolution). In the early 1990s, two different phenotypes of macrophages were described: one of them called classically activated (or inflammatory) macrophages (M1) and the other alternatively activated (or wound-healing) macrophages (M2). Currently, it is known that functional polarization of macrophages into only two groups is an over-simplified description of macrophage heterogeneity and plasticity; indeed, it is necessary to consider a continuum of functional states. Overall, the current available data indicate that macrophage polarization is a multifactorial process in which a huge number of factors can be involved producing different activation scenarios. Once a macrophage adopts a phenotype, it still retains the ability to continue changing in response to new environmental influences. The reversibility of polarization has a critical therapeutic value, especially in diseases in which an M1/M2 imbalance plays a pathogenic role. In this review, we assess the high plasticity of macrophages and their potential to be exploited to reduce chronic/detrimental inflammation. On the whole, the evidence detailed in this review underscores macrophage polarization as a target of interest for immunotherapy.

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“…Activated monocytes recruited into the site of inflammation undergo monocyte‐to‐macrophage differentiation; nevertheless, there are no definite and distinctive markers that can be used for differential discrimination of these two cell types . Certain genes such as MERTK, CD64, AXL and TYRO3 have been acknowledged to be macrophage specific; low‐level expression of macrophage‐related markers is generally observed in monocytes as well . Expression of these genes is increased in response to inflammatory factors .…”

Section: Discussionmentioning

confidence: 99%

PD‐L2⁺ wound zone macrophage‐like cells display M1/M2‐mixed activation and restrain the effector Th1 responses

et al. 2020

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Depending on the microenvironment conditions, macrophages display phenotypic and functional heterogeneity. This study characterized the programmed cell death-ligand 2 (PD-L2)-expressing macrophage-like cells drained from surgical wound zones, and investigated their influence on helper T (Th) cell responses. Although all CD14 + myeloid cells possessed macrophagelike features, CD206 + and CD163 + cells constituted a specific subpopulation with high PD-L2 expression. There was a modest correlation between the PD-L2 levels on CD206 + macrophages and the amount of interferon (IFN)-c in the drainage fluid. The adhesion-independent macrophages simultaneously presented both classically-activated M1 and alternatively-activated M2 characteristics. CD206 + and PD-L2 + cells were identified with high granularity and size, expressed arginase-1 and costimulatory molecules, had enhanced phagocytic activity and produced reactive oxygen species. The genes associated with macrophage differentiation (MERTK, AXL and TYRO3) were also upregulated. These cells provided costimulation to Th cells; yet, when PD-L2 was blocked, T-cell proliferation and IFNc production were enhanced. Under defined conditions devoid of activation stimuli and matrix adhesion, ex vivogenerated monocyte-derived macrophages displayed limited capacity to stimulate T cells. Upon exposure to IFNc, they significantly upregulated programmed death 1 ligands, especially PD-L2. These cells did not completely abrogate T-cell differentiation; however, PD-L2 checkpoint blockade restored Th1 proliferation and secretion of interleukin-2, tumor necrosis factor-a and IFNc. In conclusion, upregulation of PD-L2 on the wound zone macrophages may constitute a negative feedback loop that restrains the Th1 effector responses and avoids exacerbation of inflammation during tissue healing.

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CD64: An Attractive Immunotherapeutic Target for M1-type Macrophage Mediated Chronic Inflammatory Diseases

Cited by 74 publications

References 92 publications

Bone Marrow-Derived and Elicited Peritoneal Macrophages Are Not Created Equal: The Questions Asked Dictate the Cell Type Used

Bone Marrow-Derived and Elicited Peritoneal Macrophages Are Not Created Equal: The Questions Asked Dictate the Cell Type Used

Implications of macrophage polarization in autoimmunity

PD‐L2⁺ wound zone macrophage‐like cells display M1/M2‐mixed activation and restrain the effector Th1 responses

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CD64: An Attractive Immunotherapeutic Target for M1-type Macrophage Mediated Chronic Inflammatory Diseases

Cited by 74 publications

References 92 publications

Bone Marrow-Derived and Elicited Peritoneal Macrophages Are Not Created Equal: The Questions Asked Dictate the Cell Type Used

Bone Marrow-Derived and Elicited Peritoneal Macrophages Are Not Created Equal: The Questions Asked Dictate the Cell Type Used

Implications of macrophage polarization in autoimmunity

PD‐L2+ wound zone macrophage‐like cells display M1/M2‐mixed activation and restrain the effector Th1 responses

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Product

Resources

About

PD‐L2⁺ wound zone macrophage‐like cells display M1/M2‐mixed activation and restrain the effector Th1 responses