Targets Associated to Immuno Cell Types - Macrophages & monocytes
Jump to: GPCR | Ion Channels | Enzymes | Catalytic Receptors | Other Protein Targets |
|
The Macrophages & monocytes category includes the following Cell Ontology parent terms: |
|||
Targets Associated to Immuno Cell Types
Full documentation can be found in the GtoImmuPdb immuno cell type data documentation (PDF). ✖ | Download as CSV | ||
| GPCRs | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| β2-adrenoceptor (Adrenoceptors) |
Monocytes (CL:0000576): Monocytes from patients with rheumatoid arthritis express lower levels of β2-ARs compared with healthy subjects [12]. Monocytes from high-fat diet-induced obese mice presented higher expression levels of pro-inflammatory cytokines and a higher % of monocytes with a pro-inflammatory phenotype than those from lean animals. β2-AR stimulation induced a shift towards an anti-inflammatory activity profile and phenotype in obese mice, whereas it induced a shift towards a pro-inflammatory activity profile and phenotype in lean mice [71]. Treatment of monocytes with the β2-AR agonist clenbuterol inhibits differentiation into dendritic cells, reduces the % of CD1a+ immature DCs, while increasing the frequency of monocytes retaining CD14 surface expression [78]. Macrophages (CL:0000235): Immune cell β2-ARs are important for proinflammatory macrophage infiltration to the heart in a chronic isoprenaline administration model of heart failure. Mice lacking immune cell β2-AR have decreased proinflammatory macrophage infiltration to the heart, decreased cardiac injury and cardiomyocyte death, decreased interstitial fibrosis and hypertrophy and improved function [154]. |
|
β2-ARs are expressed on innate and adaptive immune cells of humans and rodents, and are reported to have an immuno-modulating effect [63] ... |
| FFA2 receptor (Free fatty acid receptors) |
|
FFAR2 is a GPCR activated by short-chain fatty acids, and evidence suggests that FFAR2 (and FFAR3) mediate beneficial effects associated with a fiber-rich diet. These GPCRs are of interest as targets for the treatment of inflammatory and metabolic diseases. FFAR2 is included in GtoImmuPdb as it is highly expressed on immune cells, in particular neutrophils, and evidence points to a role in diseases with dysfunctional neutrophil responses, such as inflammatory bowel disease (IBD). A Phase 2 trial of the clinical candidate GLPG0974 in ulcerative colitis has been completed (see NCT0182932). In vitro and in vivo studies suggest that the short-chain fatty acid/FFAR2 axis is modulated by metabolites of cholera toxin, that are produced by gut microbiota, which leads to enhanced mucosal antibody responses against enteric pathogen infection [179] ... |
|
| GPR65 (Class A Orphans) |
|
Tha expression profile of GPR65 suggests an immunological role. In addition, disruption of GPR65 expression leads to reduced eosinophilia in models of allergic airway disease [103] ... | |
| NK1 receptor (Tachykinin receptors) |
|
Expression in monocytes, macrophages and T helper cells suggests a role in inflammation/immunity. | |
| 5-HT2A receptor (5-Hydroxytryptamine receptors) |
Involved in chemokine production. |
|
The chemoattractant properties of 5-HT on human eosinophils is mediated by 5-HT2A receptor [25] ... |
| 5-HT1A receptor (5-Hydroxytryptamine receptors) |
Involved in phagocytosis. |
|
The chemoattractant properties of 5-HT on both human and mouse mast cells are mediated by 5-HT1A receptor [104] ... |
| 5-ht1e receptor (5-Hydroxytryptamine receptors) |
|
The expression of 5-HT1e receptors on immune cells indicates that it plays some part in immune/inflammatory responses [166] ... | |
| 5-HT2B receptor (5-Hydroxytryptamine receptors) |
Expressed by microglia. 5-HT2B receptor activation has also been shown to promote anti-inflammatory macrophage polarization. |
|
The expression of 5-HT2B receptors on immune cells indicates that it plays some part in immune/inflammatory responses [166] ... |
| 5-HT4 receptor (5-Hydroxytryptamine receptors) |
Involved in cytokine production/release from DCs. |
|
5-HT has been shown to alter cytokine production by dendritic cells via 5-HT4 and 5-HT7 receptors [2] ... |
| 5-HT7 receptor (5-Hydroxytryptamine receptors) |
5-HT7 receptor activation has been shown to promote anti-inflammatory macrophage polarization. |
|
5-HT has been shown to alter cytokine production by dendritic cells via 5-HT4 and 5-HT7 receptors [2] ... |
| 5-HT2C receptor (5-Hydroxytryptamine receptors) |
|
The expression of 5-HT2B receptors on immune cells indicates that it plays some part in immune/inflammatory responses [166] ... | |
| CXCR3 (Chemokine receptors) |
|
CXCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR3 is the receptor for CXCL9, -10 and -11, three CXC chemokines that are preferentially expressed on Th1 lymphocytes. In the cancer setting cytokines are known to establish an immunosuppressive milieu that is condusive to tumour progression. CXCR3 and its ligands have specifically been identified as being associated with this mechanism in pancreatic ductal adenocarcinoma [37] ... |
|
| C3a receptor (Complement peptide receptors) |
|
Complement C3a receptor 1 is the receptor for complement factor C3a, a component of the alternative complement cascade. It can have pro-inflammatory actions, but can also counteract the proinflammatory effects of C5a. The complement system plays a critical role intestinal immune homeostasis. In particular, C3 and the C3aR have been identified as being involved in regulating the intestinal immune response during chronic colitis [153,172] ... |
|
| HCA2 receptor (Hydroxycarboxylic acid receptors) |
Expressed in mouse monocytes. |
|
The HCA2 receptor has been identified as a molecular target of fumarate anti-inflammatory drugs in an inflammatory skin disease model [168] ... |
| S1P3 receptor (Lysophospholipid (S1P) receptors) |
S1P3 expression affects monocyte migration and macrophage activation. | ||
| Ion Channels | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| TRPC3 (Transient Receptor Potential channels (TRP)) |
TRPC channels (e.g. TRPC3, TRPC6) are involved in macrophage activation. | Expressed on B cells, T cells, neutrophils and monocytes/macrophages [130] ... | |
| KCa3.1 (Calcium- and sodium-activated potassium channels (KCa, KNa)) |
KCa3.1 and KV1.3 are the predominant potassium channels involved in regulating the hyperpolarized (negative) membrane potential which is critical for immune cell activation [56,67,120] ... | ||
| TRPM2 (Transient Receptor Potential channels (TRP)) |
TRPM2 on macrophages modulates ROS production and inflammation (including cytokine production and inflammasome activation). |
|
Expressed on human T cells, mouse dendritic cells, human and mouse neutrophils and monocytes/macrophages, and mouse mast cells [130] ... |
| TRPV2 (Transient Receptor Potential channels (TRP)) |
Expressed on mouse monocytes/macrophages, and plays a role in their chemotactic and phagocytotic processes. |
|
Expressed on human and mouse B cells, human dendritic cells and neutrophils, mouse monocytes/macrophages, and human, mouse and rat mast cells [130] ... |
| TRPM7 (Transient Receptor Potential channels (TRP), ChaK subfamily) |
In macrophages TRPM7 is involved in IL-1α production. |
|
Expressed on chicken B cells, mouse T cells, chicken monocytes/macrophages, and human mast cells [130] ... |
| Kv1.3 (Voltage-gated potassium channels (Kv)) |
Kv1.3 plays a role in macrophage function vis-a-vis proliferation and iNOS expression. |
|
Kv1.3 is involved in T cell proliferation, activation and cytokine secretion, most significantly in effector memory T lymphocytes (TEM cells) compared to naive and central memory T cells. TEM cells are major drivers of inflammation in a number of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis, so pharmacological manipulation of Kv1.3 activity may be of clinical utility in immunomodulation [1,19,46,76] ... |
| TRPM4 (Transient Receptor Potential channels (TRP)) |
TRPM4 is involved in macrophage cytokine production and phagocytosis. | TRPM4 is expressed on human T cells, mouse dendritic cells, human and mouse monocytes/macrophages, and mouse mast cells [130] ... | |
| Hv1 (Voltage-gated proton channel (Hv1)) |
Hv1 participates in ROS production by macrophages. |
|
Detection of low intracellular pH by the Hv1 ion channel impacts upon the function of B cells, macrophages, neutrophils and microglia [40,157] ... |
| Enzymes | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| FGR proto-oncogene, Src family tyrosine kinase (Src family) |
|
Fgr may be involved in neutrophil migration, potentially via binding to intergrins [18] ... | |
| HCK proto-oncogene, Src family tyrosine kinase (Src family) |
|
Hck is thought to be involved in neutrophil migration, potentially via binding to intergrins [18] ... | |
| LYN proto-oncogene, Src family tyrosine kinase (Src family) |
|
LYN is a Src family tyrosine kinase, expressed predominantly in hematopoietic cells, but also in neural, liver, and adipose tissues. LYN appears to function as a rheostat to modulate B cell signaling, and can be activating or inhibitory in action, depending on the B cell receptor and interacting protein complement present in particular cells [68,72,155] ... | |
| YES proto-oncogene 1, Src family tyrosine kinase (Src family) |
Low expression level |
|
Although primarily recognised for its oncogenic activity, we have iincluded YES1 in GtoImmuPdb based on its expression in cells of the immune system. |
| Haem oxygenase 1 (Haem oxygenase) |
|
Heme oxygenase (HO) is a rate-limiting enzyme in the catabolism of heme, catalyzing the oxidative cleavage of heme (Fe-protoporphyrin-IX) to render equimolar amounts of biliverdin, ferrous iron (Fe2+), and carbon monoxide (CO). Heme oxygenase 1 (HO1) is a Nrf2-regulated gene, whose expression is upregulated as a cytoprotective mechanism in response to cellular stresses including inflammation, ischemia, hypoxia, hyperoxia, hyperthermia, or radiation. HO1 has antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, playing an important role in the prevention of vascular inflammation and atherogenesis (reviewed in [9] ... |
|
| interleukin 1 receptor associated kinase 3 (Interleukin-1 receptor-associated kinase (IRAK) family) |
|
IRAK3 expression is restricted to monocytes and macrophages. | |
| mitogen-activated protein kinase kinase kinase 19 (STE20 subfamily) |
Expressed in alveolar and interstitial macrophages. | MAP3K19 is expressed predominantly by alveolar and interstitial macrophages and bronchial epithelial cells in the lung and is overexpressed in chronic obstructive pulmonary disease (COPD) [24] ... | |
| dual oxidase 1 (NADPH oxidases) |
DUOX1 expression has been identified in alveolar macrophages. |
|
DUOX1 participates in innate immune responses to epithelial injury and allergens, and in the development of allergic diseases [158] ... |
| mitogen-activated protein kinase kinase kinase kinase 1 (KHS subfamily) |
|
HPK1 (MAP4K1) is highly expressed in hematopoietic cell subsets. It acts as a critical negative regulator in the activation of T cells and dendritic cells [86,149] ... | |
| mitogen-activated protein kinase kinase kinase kinase 2 (KHS subfamily) |
GCK expression is upregulated in LPS-stimulated macrophages. |
|
In vitro analyses suggest that GCK plays important roles in the innate immune response and cell signalling [50] ... |
| TRPM7 (Transient Receptor Potential channels (TRP), ChaK subfamily) |
In macrophages TRPM7 is involved in IL-1α production. |
|
Expressed on chicken B cells, mouse T cells, chicken monocytes/macrophages, and human mast cells [130] ... |
| aconitate decarboxylase 1 (Itaconate biosynthesis) |
Expressed by macrophages. |
|
Itaconate (itaconic acid) is generated from the citric acid (TCA) cycle intermediate cis-aconitic acid which is produced by mitochondria. Itaconate is synthesised by the enzyme aconitate decarboxylase 1 (referred to as immunoresponsive gene 1 or IRG1). Its synthesis links metabolism to immunity and it plays an important role in the macrophage-based immune response [51,59] ... |
| Catalytic Receptors | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| MER proto-oncogene, tyrosine kinase (Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family) |
Mouse splenic macrophages, marginal zone macrophages, by immunofluorescence staining (Shao et al. 2009); mouse, mature tissue macrophages by mRNA expression (Gautier et al. 2012); mouse dendritic cells (Wallet et al. 2008, Rothlin et al. 2007) |
|
Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [20,164] ... |
| TLR6 (Toll-like receptor family) |
|
TLR6 forms heterodimers with TLR2 to detect a wide range of bacterial lipopeptides (LP) from bacterial cell membranes, and effect an immune response [65] ... | |
| Fc fragment of IgE receptor II (Fc epsilon receptors) |
Langerhans cells | FcεRII (CD23) is the low-affinity receptor for immunoglobulin E (IgE) with a Kd > 100nM. This protein is a C-type lectin found on mature B cells, activated macrophages, eosinophils, follicular dendritic cells, and platelets. It has no structural similarities with other Fc receptors. FcεRII has functions as both a membrane-bound and as a soluble receptor [97,181] ... | |
| Fc fragment of IgE receptor Ia (Fc epsilon receptors) |
Langerhans cells | The product of the FCεR1A gene is a single-pass type I membrane protein that is a high-affinity receptor for immunoglobulin E (IgE). It is the ligand binding subunit of the tetrameric FCεRI, exhibiting a Kd of ~0.1nM. | |
| single Ig and TIR domain containing (Immunoglobulin-like family of IL-1 receptors) |
Expression determined by flow cytometry in human PBMCs. |
|
IL-1R8 has been identified as a natural killer (NK) cell checkpoint that is involved in regulating NK cells' anti-viral and anti-tumour effector functions [123] ... |
| Other Protein Targets | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| CD86 (Other immune checkpoint proteins, CD molecules) |
CD86 is expressed on antigen-presenting cells. |
|
CD86 (B7-2) is a type I membrane immunoglobulin. It is expressed on antigen-presenting cells and in association with CD80 provides the costimulatory signal necessary for T cell activation and survival. CD86 interacts with CD28 or CTLA-4 on T cells. It is the interaction with CTLA-4 that is targeted ... |
| CD33 (Other immune checkpoint proteins, CD33-related SIGLECs, CD molecules) |
|
CD33 (SIGLEC3) is a myeloid cell I-type (Ig-type) lectin that binds glycans containing sialic acids [73] ... | |
| CD38 (Abscisic acid receptor complex, CD molecules) |
|
CD38 is a type II transmembrane glycoprotein, that is widely expressed on immune cells and is involved in cell adhesion and signal transduction. Its extracellular domain acts as an ectoenzyme, catalyzing the conversion of nicotinamide adenine dinucleotide (NAD+) into nicotinamide, adenosine diphosphate-ribose (ADPR), and cyclic ADPR. Expression of CD38 is tightly regulated during B-cell development and maturation [80] ... | |
| CD52 (CD molecules) |
|
CD52 (CAMPATH-1) is a short, glycosylphosphatidylinositol (GPI) anchored peptide expressed on lymphocytes and by cells of the male genital tract. CD52 is required for complement-mediated cell lysis and antibody-mediated cellular cytotoxicity. The approved monoclonal antibody, alemtuzumab ... | |
| CD74 (CD molecules) |
|
CD74 is a type II transmembrane glycoprotein which associates with the MHC class II α and β chains and directs the transport of class II molecules to lysosomal and endosomal compartments [52] ... | |
| CD80 (Other immune checkpoint proteins, CD molecules) |
|
CD80 (B7-1) is expressed on dendritic cells and activated B cells and monocytes. It is required to provide a costimulatory signal necessary for T cell activation and survival. CD80 works in concert with CD86 to prime T cells. CD80 binds CD28 and CTLA-4 on T cells. It is the interaction with CTLA-4 t ... | |
| leukocyte immunoglobulin like receptor A4 (CD85g) (CD molecules) |
|
LILRA4 (CD85g) is a member of the activating leukocyte immunoglobulin like receptor (LILRA) family (HGNC family 1181). It is involved in activation of eosinophils and homeostatic regulation of the innate immunity of plasmacytoid dendritic cells (pDCs) [39] ... | |
| CS1 (CD319) (CD molecules) |
|
CS1 is a member of the signalling lymphocyte activation molecule (SLAM) receptor family. CS1 is a membrane glycoprotein primarily expressed on plasma cells. Homophilic interaction (i.e. interaction with itself) of CS1 induces B cell proliferation and autocrine cytokine secretion, thus playing a role in various immune functions. CS1 is a validated molecular target for the development of novel immunotherapeutics with the potential to treat MM, a malignant disease of plasma cells which remains incurable despite advances in treatment (such as bortezomib, lenalidomide and immunotherapies in clinical trial). Indeed, a combination therapy containing the anti-CS1 mAb elotuzumab (elotuzumab + lenalidomide + dexamethasone), was FDA approved for MM in 2015. CS1 expression is also elevated in patients with systemic lupus erythematosus (SLE) [100] ... |
|
| CD209 molecule (C-type lectin-like receptors (CLRs)) |
DC-SIGN is a pathogen-recognition receptor involved in initiating the primary immune response to various viral and bacterial pathogens, as well as antigen presentation and initiation of the adaptive immune response. | ||
| C-type lectin domain family 7 member A (C-type lectin-like receptors (CLRs)) |
Dectin-1 is widely expressed in macrophage populations. | Dectin-1 is a pattern recognition receptor involved in initiating the innate immune response upon recognition of various β(1,3)-linked and β(1,6)-linked glucans from fungi and plants. It mediates phagocytosis and the production of inflammatory mediators [31] ... | |
| C-type lectin domain family 4 member E (C-type lectin-like receptors (CLRs)) |
|
Mincle is an FcRγ-associated membrane receptor involved in initiating the innate immune response upon recognition of endogenous and exogenous ligands including Sin3A-associated protein (SAP130), α-mannan on fungal cell walls and mycobacterial cord factor (trehalose-6,6′-dimycolate (TDM)) [32] ... | |
| regulator of G-protein signaling 1 (R4 family) |
|
RGS1 is expressed in lymphocytes and macrophages and plays a role in leukocyte trafficking and vascular inflammation [27,81,124,131] ... | |
| B7-H3 (CD276) (Other immune checkpoint proteins, CD molecules) |
B7-H3 expression is induced in monocytes by inflammatory cytokines and by phorbol myristate acetate/ionomycin exposure [47]. |
|
B7-H3 is an immunoregulatory receptor involved in T cell activation and IFN-γ production [47,60] ... |
| chitinase 3 like 1 (Chitinase-like proteins) |
Highly expressed in macropahges (detected by mRNA expression). |
|
CHI3L1 is recognised as a proinflammatory mediator in the development and progression of Th2 inflammation, such as in allergic reactions [35] ... |
| Fc fragment of IgA receptor (Immunoglobulin like domain containing proteins, CD molecules) |
FcαRI (CD89) is constitutively expressed on monocytes/macrophages. |
|
FcαRI is the cognate receptor for immunoglobulin A (IgA). In humans, IgA is predominantly expressed in the intestine, where it is important for maintaining mucosal homeostasis. IgA serves as a first-line defence to protect the gut epithelium from pathogens and enteric toxins [117,129] ... |
| CD4 (CD molecules) |
CD4 is being targeted for clinical utility in inflammatory diseases like rheumatoid arthritis (RA), neoplasms derived from T helper cells (T cell lymphomas and related malignancies), and for anti-HIV potential. Depending on the design of CD4 targeting antibodies, they can produce immunosuppressive effects via activation of Tregs and induction of tolerance, block HIV binding to CD4 to prevent HIV infection, or induce depletion of CD4+ T cells by apoptosis, ADCC, or CDC [102,163] ... | ||
| leukocyte immunoglobulin like receptor B1 (CD85j) (CD molecules, Other immune checkpoint proteins) |
Expression of LILRB1 by macrophages mediates an inhibitory signal that negatively regulates phagocytosis [15]. The protective effect of LILRB1 expression is exploited by some cancers, to avoid immune system-mediated destruction. |
|
LILRB1 (CD85j) is a member of the inhibitory leukocyte immunoglobulin like receptor (LILRB) family (HGNC family 1182). It acts as an inhibitory immune checkpoint for B cell function. Ligands identified for LILRB include native MHC class I proteins, some HLA molecules, pathogen-derived ligands (e.g. from CMV, Dengue virus and some bacteria) and host immunomodulatory proteins such as S100 calcium binding protein A9 (S100A9; P06702; which also binds TLR4 and RAGE) [33] ... |
| C-type lectin domain family 12 member A (C-type lectin-like receptors (CLRs)) |
|
The CLEC12A protein is a negative regulator of granulocyte and monocyte function [82,118] ... | |
| S100 calcium binding protein A11 (EF-hand domain containing proteins) |
S100A11 is released by circulating mononuclear cells. The specific cell type(s) has not been fully determined. Elevated levels are detected in patients with SLE (circulating plasma level) [42] and RA (in synovial tissues and fluid) [6]. |
|
S100A11 is a pro-inflammatory calcium-binding protein. Elevated S100A11 has been reported as a marker of disease activity and extramuscular manifestations in inflammatory myopathies [5] ... |
| CD36 molecule (CD36 blood group) (CD molecules) |
|
CD36 expressed by macrophages plays a key role in the recognition and phagocytosis (scavenging) of multiple ligands that are recognised either as damage-associated molecular patterns (DAMPs) released by apoptotic cells, or as potentially dangerous pathogen-associated ligands. CD36 associates with specific Toll-like receptor (TLR) DAMP-detecting heterodimers when bound by certain ligands, and following internalisation of the ligand/CD36/TLR clusters, inflammatory responses (e.g. NF-κB-dependent production of CXCL1, CXCL2, CCL9 and CCL5, NLRP3 inflammasome-mediated IL-1B production, and NF-κB-dependent production of TNF in reponse to microbial diacylated lipopeptide) are triggered. Pharmacological modulation of CD36/TLR signalling is being explored as a strategy to suppress macrophage-driven inflammation [53,156,182] ... | |
| CD14 molecule (CD molecules) |
|
Because of its key role in amplifying the immune response, CD14 was targeted for pharmacological modulation. Implicit Bioscience developed a first-in-class anti-CD14 monoclonal antbody (atibuclimab; IC14) as a clinical lead [151,162] ... | |
| regulator of G-protein signaling 10 (R12 family) |
|
||
