Silencing LAIR-1 in human THP-1 macrophage increases foam cell formation by modulating PPARγ and M2 polarization

Yi, Xin; Zhang, Jinxue; Zhuang, Ran; Wang, Song; Cheng, Shiyang; Zhang, Dongliang; Xie, Jiangang; Hu, Wei; Liu, Xueqin; Zhang, Yun; Ding, Yong; Zhang, Yuan

doi:10.1016/j.cyto.2018.08.028

Cited by 20 publications

(13 citation statements)

References 47 publications

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“…The LAIR-1 KD data showed that the higher expression of LAIR-1 decreased the average amount of cellular uptake on both control and LAIR1-LP surfaces ( Figure 4B). These findings are consistent with published literature showing that knockdown of LAIR-1 increased the uptake of lipids (Yi et al, 2018). However, knocking down LAIR-1 expression arrested the anti-inflammatory effects (TNFα levels) of LAIR1-LP on M1-stimulated BMDMs, which is consistent with previously published results (Kim et al, 2017).…”

Section: Discussionsupporting

confidence: 93%

“…Gene expression of CD36, SRA-1, integrin β2, and β-actin were examined, and all were significantly increased ( Figure 5A). It has been shown in previously published studies that gene and protein expression of LAIR-1, CD-36, and SRA-1 are positively correlated (Zibara et al, 2002;Yi et al, 2018). F4/80, a surface marker for macrophages but is not known to be linked to uptake, was the control and showed no increase in expression.…”

Section: Knockdown (Kd) Of Lair-1 Expression In Bmdm and Its Effect Omentioning

confidence: 88%

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Effects of Surface-Bound Collagen-Mimetic Peptides on Macrophage Uptake and Immunomodulation

Rowley

Meli

Wu-Woods

et al. 2020

Front. Bioeng. Biotechnol.

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The interaction between collagen/collagen-like peptides and the commonly expressed immune cell receptor LAIR-1 (leukocyte-associated immunoglobulin-like receptor-1) regulates and directs immune responses throughout the body. Understanding and designing these interactions within the context of biomaterials could advance the development of materials used in medical applications. In this study, we investigate the immunomodulatory effects of biomaterials engineered to display a human collagen III-derived ligand peptide (LAIR1-LP) that targets LAIR-1. Specifically, we examine the effects of LAIR1-LP functionalized surfaces on uptake of polymeric particles and cell debris by macrophages polarized toward inflammatory or healing phenotypes. We observed that culture of macrophages on LAIR1-LP functionalized surfaces increased their uptake of PLGA micro-and nano-particles, as well as apoptotic fibroblasts, while reducing their secretion of TNFα in response to LPS/IFNγ pro-inflammatory stimulation, when compared to cells seeded on control surfaces. To investigate the role of LAIR-1 in the observed LAIR1-LP-induced effects, we used siRNA to knock down LAIR-1 expression and found that cells lacking LAIR-1 exhibited enhanced particle uptake on LAIR1-LP and control surfaces. Furthermore, analysis of gene expression showed that LAIR-1 knockdown led to increase expression of other receptors involved in cell uptake, including CD-36, SRA-1, and beta-2 integrin. Together, our study suggests that LAIR1-LP enhances macrophage uptake potentially through interactions with collagen-domain binding surface receptors, and inhibits inflammation through interaction with LAIR-1.

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Section: Discussionsupporting

confidence: 93%

Section: Knockdown (Kd) Of Lair-1 Expression In Bmdm and Its Effect Omentioning

confidence: 88%

Effects of Surface-Bound Collagen-Mimetic Peptides on Macrophage Uptake and Immunomodulation

Rowley

Meli

Wu-Woods

et al. 2020

Front. Bioeng. Biotechnol.

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“…LAIR1 (CD305) is an inhibitory collagen receptor expressed by certain blood cells, e.g., by monocytes. As demonstrated by Yi et al, silencing of LAIR1 in immortalized human monocytes facilitates M2 polarization indicated by increased expression of ARG1 and CD206 [ 29 ]. This study identifies LAIR1 as a promising therapeutic target in atherosclerosis and related disorders.…”

Section: Macrophages As Perfect Cells For Reprogrammingmentioning

confidence: 99%

Macrophage Modification Strategies for Efficient Cell Therapy

Poltavets

Vishnyakova

Elchaninov

et al. 2020

Cells

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Macrophages, important cells of innate immunity, are known for their phagocytic activity, capability for antigen presentation, and flexible phenotypes. Macrophages are found in all tissues and therefore represent an attractive therapeutic target for the treatment of diseases of various etiology. Genetic programming of macrophages is an important issue of modern molecular and cellular medicine. The controllable activation of macrophages towards desirable phenotypes in vivo and in vitro will provide effective treatments for a number of inflammatory and proliferative diseases. This review is focused on the methods for specific alteration of gene expression in macrophages, including the controllable promotion of the desired M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes in certain pathologies or model systems. Here we review the strategies of target selection, the methods of vector delivery, and the gene editing approaches used for modification of macrophages.

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“…Overall, most current studies considered macrophages or NK cells to be the major effector cells in innate checkpoint-blockade antibody therapy ( 223 – 225 ). Given that neutrophils are endowed with similar inhibitory receptors, they can potentially acquire a supporting anti-tumor response.…”

Section: Targeting Neutrophil Activity In Cancer Therapymentioning

confidence: 99%

Plasticity in Pro- and Anti-tumor Activity of Neutrophils: Shifting the Balance

et al. 2020

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Over the last decades, cancer immunotherapies such as checkpoint blockade and adoptive T cell transfer have been a game changer in many aspects and have improved the treatment for various malignancies considerably. Despite the clinical success of harnessing the adaptive immunity to combat the tumor, the benefits of immunotherapy are still limited to a subset of patients and cancer types. In recent years, neutrophils, the most abundant circulating leukocytes, have emerged as promising targets for anti-cancer therapies. Traditionally regarded as the first line of defense against infections, neutrophils are increasingly recognized as critical players during cancer progression. Evidence shows the functional plasticity of neutrophils in the tumor microenvironment, allowing neutrophils to exert either pro-tumor or anti-tumor effects. This review describes the tumor-promoting roles of neutrophils, focusing on their myeloid-derived suppressor cell activity, as well as their role in tumor elimination, exerted mainly via antibody-dependent cellular cytotoxicity. We will discuss potential approaches to therapeutically target neutrophils in cancer. These include strategies in humans to either silence the pro-tumor activity of neutrophils, or to activate or enhance their anti-tumor functions. Redirecting neutrophils seems a promising approach to harness innate immunity to improve treatment for cancer patients.

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Silencing LAIR-1 in human THP-1 macrophage increases foam cell formation by modulating PPARγ and M2 polarization

Cited by 20 publications

References 47 publications

Effects of Surface-Bound Collagen-Mimetic Peptides on Macrophage Uptake and Immunomodulation

Effects of Surface-Bound Collagen-Mimetic Peptides on Macrophage Uptake and Immunomodulation

Macrophage Modification Strategies for Efficient Cell Therapy

Plasticity in Pro- and Anti-tumor Activity of Neutrophils: Shifting the Balance

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