ERMAP is a B7 family-related molecule that negatively regulates T cell and macrophage responses

Su, Min; Lin, Yujun; Cui, Cheng; Tian, Xiaohong; Lai, Laijun

doi:10.1038/s41423-020-0494-8

Cited by 17 publications

(17 citation statements)

References 60 publications

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“…Macrophages can be divided into two distinct subsets, the classically activated M1 and alternatively activated M2 macrophages 30 . M1 macrophages are proinflammatory, whereas M2 macrophages are anti-inflammatory.…”

Section: Resultsmentioning

confidence: 99%

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BTN2A2 protein negatively regulates T cells to ameliorate collagen-induced arthritis in mice

Luo

et al. 2021

Sci Rep

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Rheumatoid arthritis (RA) is an autoimmune disorder characterized by persistent inflammatory responses in target tissues and organs, resulting in the destruction of joints. Collagen type II (CII)-induced arthritis (CIA) is the most used animal model for human RA. Although BTN2A2 protein has been previously shown to inhibit T cell functions in vitro, its effect on autoimmune arthritis has not been reported. In this study, we investigate the ability of a recombinant BTN2A2-IgG2a Fc (BTN2A2-Ig) fusion protein to treat CIA. We show here that administration of BTN2A2-Ig attenuates established CIA, as compared with control Ig protein treatment. This is associated with reduced activation, proliferation and Th1/Th17 cytokine production of T cells in BTN2A2-Ig-treated CIA mice. BTN2A2-Ig also inhibits CII-specific T cell proliferation and Th1/Th17 cytokine production. Although the percentage of effector T cells is decreased in BTN2A2-Ig-treated CIA mice, the proportions of naive T cells and regulatory T cells is increased. Furthermore, BTN2A2-Ig reduces the percentage of proinflammatory M1 macrophages but increases the percentage of anti-inflammatory M2 macrophages in the CIA mice. Our results suggest that BTN2A2-Ig protein has the potential to be used in the treatment of collagen-induced arthritis models.

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Section: Resultsmentioning

confidence: 99%

“…The endotoxin level of the recombinant protein was < 0.01 EU/ml pig-1 of purified protein as determined by the endpoint chromogenic LAL test. Control Ig (recombinant mouse IgG2a Fc protein) was purchased from BXCell (West Lebanon, NH) 30 .…”

Section: Methodsmentioning

confidence: 99%

BTN2A2 protein negatively regulates T cells to ameliorate collagen-induced arthritis in mice

Luo

et al. 2021

Sci Rep

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“…On the other hand, in autoimmune diseases, the immune system actively attacks and destroys the self-tissues. In order to elicit protective immunity against cancer and infection and inhibit the overactivity of the immune system, immune responses need to be strictly controlled by the B7 family members, which contain co-stimulatory and co-inhibitory molecules [ 5 , 6 ]. T cells are introduced as central elements of adaptive immunity, and their activation depends on two signals: signal 1, or antigen recognition, where peptides presented by the main histocompatibility complex (MHC) are identified by T cell receptors (TCRs), and signal 2, or co-stimulation, involving the combination of co-regulators such as B7 proteins, consisting of co-stimulatory and co-inhibitory molecules expressed on antigen-presenting cells (APC).…”

Section: Introductionmentioning

confidence: 99%

The Positive and Negative Immunoregulatory Role of B7 Family: Promising Novel Targets in Gastric Cancer Treatment

Bolandi

Derakhshani

Hemmat

et al. 2021

IJMS

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Gastric cancer (GC), with a heterogeneous nature, is the third leading cause of death worldwide. Over the past few decades, stable reductions in the incidence of GC have been observed. However, due to the poor response to common treatments and late diagnosis, this cancer is still considered one of the lethal cancers. Emerging methods such as immunotherapy with immune checkpoint inhibitors (ICIs) have transformed the landscape of treatment for GC patients. There are presently eleven known members of the B7 family as immune checkpoint molecules: B7-1 (CD80), B7-2 (CD86), B7-H1 (PD-L1, CD274), B7-DC (PDCD1LG2, PD-L2, CD273), B7-H2 (B7RP1, ICOS-L, CD275), B7-H3 (CD276), B7-H4 (B7x, B7S1, Vtcn1), B7-H5 (VISTA, Gi24, DD1α, Dies1 SISP1), B7-H6 (NCR3LG1), B7-H7 (HHLA2), and Ig-like domain-containing receptor 2 (ILDR2). Interaction of the B7 family of immune-regulatory ligands with the corresponding receptors resulted in the induction and inhibition of T cell responses by sending co-stimulatory and co-inhibitory signals, respectively. Manipulation of the signals provided by the B7 family has significant potential in the management of GC.

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“…Recognizing the importance of the B7 family in controlling immune responses, we performed a series of genome-wide database searches to find molecules that are homologous to known B7 family members. We have discovered that erythroid membrane-associated protein (ERMAP) shares sequence and structural similarities with the known B7 family members [ 16 ]. We have shown that the ERMAP receptor is expressed on T cells and macrophages [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

“…We have discovered that erythroid membrane-associated protein (ERMAP) shares sequence and structural similarities with the known B7 family members [ 16 ]. We have shown that the ERMAP receptor is expressed on T cells and macrophages [ 16 ]. ERMAP protein inhibits T cell functions and increases the generation of anti-inflammatory M2 macrophages, whereas anti-ERMAP antibody neutralizes the T cell inhibitory activity of ERMAP and enhances macrophage phagocytosis ability [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Administration of anti-ERMAP antibody ameliorates Alzheimer’s disease in mice

Liu

Zhao

Lin

et al. 2021

J Neuroinflammation

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Background Alzheimer’s disease (AD) is a devastating age-related neurodegenerative disorder and characterized by progressive loss of memory and cognitive functions, which are associated with amyloid-beta (Aβ) plaques. Immune cells play an important role in the clearance of Aβ deposits. Immune responses are regulated by immune regulators in which the B7 family members play a crucial role. We have recently identified erythroid membrane-associated protein (ERMAP) as a novel B7 family-related immune regulator and shown that ERMAP protein affects T cell and macrophage functions. Methods We produced a monoclonal antibody (mAb) against ERMAP protein and then determined the ability of the mAb to affect cognitive performance and AD pathology in mice. Results We have shown that the anti-ERMAP mAb neutralizes the T cell inhibitory activity of ERMAP and enhances macrophages to phagocytose Aβ in vitro. Administration of the mAb into AD mice improves cognitive performance and reduces Aβ plaque load in the brain. This is related to increased proportion of T cells, especially IFNγ-producing T cells, in the spleen and the choroid plexus (CP), enhanced expression of immune cell trafficking molecules in the CP, and increased migration of monocyte-derived macrophages into the brain. Furthermore, the production of anti-Aβ antibodies in the serum and the macrophage phagocytosis of Aβ are enhanced in the anti-ERMAP mAb-treated AD mice. Conclusions Our results suggest that manipulating the ERMAP pathway has the potential to provide a novel approach to treat AD patients.

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ERMAP is a B7 family-related molecule that negatively regulates T cell and macrophage responses

Cited by 17 publications

References 60 publications

BTN2A2 protein negatively regulates T cells to ameliorate collagen-induced arthritis in mice

BTN2A2 protein negatively regulates T cells to ameliorate collagen-induced arthritis in mice

The Positive and Negative Immunoregulatory Role of B7 Family: Promising Novel Targets in Gastric Cancer Treatment

Administration of anti-ERMAP antibody ameliorates Alzheimer’s disease in mice

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