SIRPα: A key player in innate immunity

Abstract

Signal regulatory protein alpha (SIRPα) is a crucial inhibitory regulator expressed on the surface of myeloid cells, including macrophages, dendritic cells (DCs), monocytes, neutrophils and microglia. SIRPα plays an indispensable role in innate immune and adoptive immune responses in cancer immunology, tissue homeostasis and other physiological or phycological conditions. This review provides an overview of the research history, ligands, signal transduction pathways and functional mechanisms associated with SIRPα. Additionally, we summarize the therapeutic implications of targeting SIRPα as a promising novel strategy in immuno‐oncology.This article is protected by copyright. All rights reserved

Diet-responsive proteogenomic effects following short-term restriction of animal products in humans

“…For 22 proteins the top cis-pQTL explained over 50% of the variance, underscoring the presence of strong cis-regulatory effects. For example, rs72620873, a cis-pQTL shared between all contexts, explained ∼ 59% of the variance in levels of SIRPA, an immune receptor that maintains self-tolerance and is linked to cancer, transplant rejection, autoimmunity, and neurodegeneration when dysregulated 14 .…”

Diet-responsive proteogenomic effects following short-term restriction of animal products in humans

“…For 22 proteins the top cis-pQTL explained over 50% of the variance, underscoring the presence of strong cis-regulatory effects. For example, rs72620873, a cis-pQTL shared between all contexts, explained ∼ 59% of the variance in levels of SIRPA, an immune receptor that maintains self-tolerance and is linked to cancer, transplant rejection, autoimmunity, and neurodegeneration when dysregulated 14 .…”

Seeking rhythmic patterns in microglial cells within the circadian pineal gland from male rats

“…The precise regulation of microglial phagocytosis is indispensable to prevent uncontrolled elimination of cellular elements, which could potentially lead to neurodegeneration (Butler et al, 2021). Activation of modulatory receptors, such as signal regulatory protein alpha (SIRP alpha), initiates signaling pathways in microglial cells that suppress their phagocytic capacity (Feng et al, 2023; Zhang et al, 2015). Notably, SIRP alpha transcript levels have been shown to be upregulated at daytime compared to nighttime in α-microglia from the rat PG (Mays et al, 2018).…”

Noninvasive Monitoring of Inflammatory Processes by Myeloid Cell–Directed PET Tracers in an Experimental Severe Acute Respiratory Syndrome Coronavirus 2 Infection Model

“…Several groups indicate that TSPO is preferentially upregulated in antiinflammatory macrophages, which are subject of depletion during the inflammatory process associated with SARS-CoV-2 ( 24 – 26 ) . In contrast, SIRPα represents a broader pan-myeloid cell surface marker, including monocytes, macrophages, natural killer cells, neutrophils, and dendritic cells ( 15 ) . [ 64 Cu]Cu-SIRPα-Nb also binds cSIRPγ, which is expressed, to a lower extent, on human and NHP T cells ( 27 ) .…”

Diet-responsive proteogenomic effects following short-term restriction of animal products in humans

“…For 22 proteins the top cis-pQTL explained over 50% of the variance, underscoring the presence of strong cis-regulatory effects. For example, rs72620873, a cis-pQTL shared between all contexts, explained ∼ 59% of the variance in levels of SIRPA, an immune receptor that maintains self-tolerance and is linked to cancer, transplant rejection, autoimmunity, and neurodegeneration when dysregulated 14 .…”

Seeking rhythmic patterns in microglial cells within the circadian pineal gland from male rats

“…The precise regulation of microglial phagocytosis is indispensable to prevent uncontrolled elimination of cellular elements, which could potentially lead to neurodegeneration (Butler et al, 2021). Activation of modulatory receptors, such as signal regulatory protein alpha (SIRP alpha), initiates signaling pathways in microglial cells that suppress their phagocytic capacity (Feng et al, 2023; Zhang et al, 2015). Notably, SIRP alpha transcript levels have been shown to be upregulated at daytime compared to nighttime in α-microglia from the rat PG (Mays et al, 2018).…”

Noninvasive Monitoring of Inflammatory Processes by Myeloid Cell–Directed PET Tracers in an Experimental Severe Acute Respiratory Syndrome Coronavirus 2 Infection Model

“…Several groups indicate that TSPO is preferentially upregulated in antiinflammatory macrophages, which are subject of depletion during the inflammatory process associated with SARS-CoV-2 ( 24 – 26 ) . In contrast, SIRPα represents a broader pan-myeloid cell surface marker, including monocytes, macrophages, natural killer cells, neutrophils, and dendritic cells ( 15 ) . [ 64 Cu]Cu-SIRPα-Nb also binds cSIRPγ, which is expressed, to a lower extent, on human and NHP T cells ( 27 ) .…”

Diet-responsive proteogenomic effects following short-term restriction of animal products in humans

“…For 22 proteins the top cis-pQTL explained over 50% of the variance, underscoring the presence of strong cis-regulatory effects. For example, rs72620873, a cis-pQTL shared between all contexts, explained ∼ 59% of the variance in levels of SIRPA, an immune receptor that maintains self-tolerance and is linked to cancer, transplant rejection, autoimmunity, and neurodegeneration when dysregulated 14 .…”

Seeking rhythmic patterns in microglial cells within the circadian pineal gland from male rats

“…The precise regulation of microglial phagocytosis is indispensable to prevent uncontrolled elimination of cellular elements, which could potentially lead to neurodegeneration (Butler et al, 2021). Activation of modulatory receptors, such as signal regulatory protein alpha (SIRP alpha), initiates signaling pathways in microglial cells that suppress their phagocytic capacity (Feng et al, 2023; Zhang et al, 2015). Notably, SIRP alpha transcript levels have been shown to be upregulated at daytime compared to nighttime in α-microglia from the rat PG (Mays et al, 2018).…”

Noninvasive Monitoring of Inflammatory Processes by Myeloid Cell–Directed PET Tracers in an Experimental Severe Acute Respiratory Syndrome Coronavirus 2 Infection Model

“…Several groups indicate that TSPO is preferentially upregulated in antiinflammatory macrophages, which are subject of depletion during the inflammatory process associated with SARS-CoV-2 ( 24 – 26 ) . In contrast, SIRPα represents a broader pan-myeloid cell surface marker, including monocytes, macrophages, natural killer cells, neutrophils, and dendritic cells ( 15 ) . [ 64 Cu]Cu-SIRPα-Nb also binds cSIRPγ, which is expressed, to a lower extent, on human and NHP T cells ( 27 ) .…”