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Activation of the myeloid checkpoint inhibitor LILRB3 (ILT5) elicits profound immununomodulation

ABSTRACT: Activation of the myeloid checkpoint inhibitor LILRB3 (ILT5) elicits profound immununomodulation

PROVIDER: PRJNA636812 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11908871.fastq.gz	Fastqsanger.gz
	SRR11908872.fastq.gz	Fastqsanger.gz
	SRR11908873.fastq.gz	Fastqsanger.gz
	SRR11908874.fastq.gz	Fastqsanger.gz
	SRR11908875.fastq.gz	Fastqsanger.gz

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Activation of the myeloid checkpoint inhibitor LILRB3 (ILT5) elicits profound immununomodulation

Project description:Purpose:To investigate the potential immunomodulatory function of a new panel of LILRB3-specific monoclonal antibody

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LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation.

Project description:Despite advances in identifying the key immunoregulatory roles of many of the human leukocyte immunoglobulin-like receptor (LILR) family members, the function of the inhibitory molecule LILRB3 (ILT5, CD85a, LIR3) remains unclear. Studies indicate a predominant myeloid expression; however, high homology within the LILR family and a relative paucity of reagents have hindered progress toward identifying the function of this receptor. To investigate its function and potential immunomodulatory capacity, a panel of LILRB3-specific monoclonal antibodies (mAbs) was generated. LILRB3-specific mAbs bound to discrete epitopes in Ig-like domain 2 or 4. LILRB3 ligation on primary human monocytes by an agonistic mAb resulted in phenotypic and functional changes, leading to potent inhibition of immune responses in vitro, including significant reduction in T cell proliferation. Importantly, agonizing LILRB3 in humanized mice induced tolerance and permitted efficient engraftment of allogeneic cells. Our findings reveal powerful immunosuppressive functions of LILRB3 and identify it as an important myeloid checkpoint receptor.

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Project description:To explore the downstream signaling of the LILRB3 receptor, agonist and antagonist antibodies were used. As the LILRB3 ligand remains unknown, antibody mediated signalling is our best means of further ellucidating the mechanisms of LILRB3. This study explores LILRB3 in the context of AML, using the u937 cell line as a model.

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Single-cell RNA sequencing of PBMC with and without LILRB3-4SNPs pretransplant and posttransplant

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Project description:RNA sequencing were conducted on 20 transplant patients with (n=10) and without (n=10) LILRB3-4SNPs risk allele 3 months after kidney transplantation to evaluate the potential effects of this SNP on post-transplant blood.

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The Paired Orphan Immune Receptors LILRA6 and LILRB3 Modulate Fc Receptor Mediated Functions of Neutrophils

Project description:to characterise expression of LILRA6/LILRB3 receptors during neutrophil differentiation and activation, and to characterise their roles in modulating Fc receptor mediated effector functions.

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LILRB3 agonism and antagonism using monocolonal antibodies

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