Targets Associated to Immuno Cell Types - Granulocytes
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The Granulocytes category includes the following Cell Ontology parent terms: |
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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 |
| H1 receptor (Histamine receptors) |
Eosinophils express all four histamine receptor subtypes. |
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The H1 receptor was the first of the family to be targeted for clinical use, with antagonists (anti-histamines) developed that are still used widely to treat allergic inflammation such as rhinitis, allergic conjunctivitis, urticaria and even anaphylaxis. |
| H2 receptor (Histamine receptors) |
Eosinophils express all four histamine receptor subtypes. |
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Histamine action via the H2 receptor inhibits eosinophil, mast cell and neutrophil chemotaxis, IL-12 production by dendritic cells and also suppresses Th2 cells and cytokine formation. In airway inflammation the H2 receptor mediates bronchial smooth muscle relaxation, vasodilation and mucus production [105] ... |
| H3 receptor (Histamine receptors) |
Eosinophils express all four histamine receptor subtypes. |
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H3 receptor expression is low in peripheral tissues, but high in neuronal mast cells and eosinophils. It is not currently considered an important target in allergy. |
| H4 receptor (Histamine receptors) |
Eosinophils express all four histamine receptor subtypes. |
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H4 receptor is primarily expressed in mast cells and eosinophils, but is also found on human neutrophils and basophils, and plays an important role in modulating eosinophil chemotaxis [98,145] ... |
| CCR3 (Chemokine receptors) |
CCR3 is highly expressed on eosinophils, and is the promary receptor mediating their differentiation, chemotaxis and degranulation. It is also expressed on basophils, mast cells, and Th2 lymphocytes. |
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CCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. |
| S1P1 receptor (Lysophospholipid (S1P) receptors) |
Eosinophils express all S1P receptors except S1P2R. |
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S1P1R activation by agonists downregulates allergic inflammation (i.e. it has an inhibitory effect) [53,55,115] ... |
| S1P3 receptor (Lysophospholipid (S1P) receptors) |
Eosinophils express all S1P receptors except S1P2R. |
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| S1P4 receptor (Lysophospholipid (S1P) receptors) |
Eosinophils express all S1P receptors except S1P2R. A missense variant of S1P4 receptor in humans correlates with decreased circulating neutrophils. |
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| CB2 receptor (Cannabinoid receptors) |
Eosinophils do not express CB1 receptor. |
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CB2 receptor on eosinophils mainly mediates anti-inflammatory and immunomodulatory actions e.g. downregulation of pro-inflammatory mediator release. Pharmacological targeting with the CB2 receptor selective antagonist SR144528 attenuates the recruitment of eosinophils and ear swelling in a murine chronic contact dermatitis model [100] ... |
| B1 receptor (Bradykinin receptors) |
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Bradykinin ... | |
| B2 receptor (Bradykinin receptors) |
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Bradykinin is a vasoactive, pain inducing and pro-inflammatory (phlogistic) kinin released during acute inflammation, and its receptors, B1 and B2, are expressed on eosinophils, and neutrophils. The B2 receptor antagonist icatibant was evaluated in a Phase 2 trial for osteoarthritis [32] ... | |
| FFA2 receptor (Free fatty acid receptors) |
FFA2 receptor is selectively expressed by leukocytes, especially neutrophils. |
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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 [141] ... |
| 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 [74] ... | ||
| 5-HT2A receptor (5-Hydroxytryptamine receptors) |
Involved in chemotaxis. |
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The chemoattractant properties of 5-HT on human eosinophils is mediated by 5-HT2A receptor [17] ... |
| 5-HT7 receptor (5-Hydroxytryptamine receptors) |
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5-HT has been shown to alter cytokine production by dendritic cells via 5-HT4 and 5-HT7 receptors [2] ... | |
| C3a receptor (Complement peptide receptors) |
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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 [121,134] ... |
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| 5-HT1B receptor (5-Hydroxytryptamine receptors) |
Expressed by eosinophils. |
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The expression of 5-HT1B receptors on immune cells indicates that it plays some part in immune/inflammatory responses [130] ... |
| 5-ht1e receptor (5-Hydroxytryptamine receptors) |
Expressed by eosinophils. |
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The expression of 5-HT1e receptors on immune cells indicates that it plays some part in immune/inflammatory responses [130] ... |
| 5-HT2B receptor (5-Hydroxytryptamine receptors) |
Expressed by eosinophils. |
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The expression of 5-HT2B receptors on immune cells indicates that it plays some part in immune/inflammatory responses [130] ... |
| DP2 receptor (Prostanoid receptors) |
Expression of the DP2 receptor is restricted to eosinophils, basophils, Th2 cells, and innate lymphoid cells. |
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The DP2 receptor (a.k.a. CRTH2, chemoattractant receptor-homologous molecule expressed on T-helper 2 cells) is expressed exclusively by a range of human immune cells including Th2 cells, basophils, eosinophils and innate lymphoid cells [52,95] ... |
| FPR1 (Formylpeptide receptors) |
FPR1 on neutrophils is a physiologically relevant plague receptor. It is exploited by Y. pestis to deliver effector proteins of the bacterium's conserved type III secretion system to host cells. |
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The primary function of FPR1 is recognition of formylpeptides. Detection of bacterial N-formylpeptides via FPR1 activates immune-cell chemotaxis and cytokine release, making this GPCR an important component of the host defense mechanism. Osei-Owusu et al. (2019) demonstrated that FPR1 on immune cells is the target of the needle cap protein (LcrV; Uniprot accession P0C7U7) of Yersinia pestis (the plague bacterium), via which the bacteria destroy host immune cells [102] ... |
| HCA2 receptor (Hydroxycarboxylic acid receptors) |
Expressed in mouse neutrophils. |
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The HCA2 receptor has been identified as a molecular target of fumarate anti-inflammatory drugs in an inflammatory skin disease model [132] ... |
| ADGRG5 (Adhesion Class GPCRs) |
Amongst immune cells types, ADGRG5 is expressed primarily by granulocytes such as eosinophils. |
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| 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 chemotaxis, LTC4 secretion and PAF signalling | Expressed on B cells, T cells, neutrophils and monocytes/macrophages [104] ... | |
| P2X1 (P2X receptors) |
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Functional P2X1 receptors are expressed by healthy human eosinophils [139] ... | |
| Hv1 (Voltage-gated proton channel (Hv1)) |
Hv1 participates in ROS production by neutrophils. |
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Detection of low intracellular pH by the Hv1 ion channel impacts upon the function of B cells, macrophages, neutrophils and microglia [24,125] ... |
| TRPV2 (Transient Receptor Potential channels (TRP)) |
Expressed on human neutrophils. |
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Expressed on human and mouse B cells, human dendritic cells and neutrophils, mouse monocytes/macrophages, and human, mouse and rat mast cells [104] ... |
| Enzymes | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| cathepsin C (C1: Papain) |
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Cathepsin C (CatC) is a lysosomal cysteine protease that is constitutively expressed at high levels in lung, kidney, liver and spleen. As well as activity in lysosomal protein degradation, cathepsin C also plays a key role in the activation of granule serine proteases in cytotoxic T cells, natural killer cells (granzymes A and B), mast cells (chymase and tryptase) and neutrophils (cathepsin G, neutrophil elastase, proteinase 3). Dysregulated activation of neutrophil elastase at inflammatory sites induces the release of pro-inflammatoy mediators and can lead to acute tissue injury. This mechanism is recognised as causing lung damage in neutrophil driven conditions such as asthma and COPD, and has driven the pharmaceutical industry to search for cathepsin C inhibitors with clinical utility (e.g. brensocatib; formerly AZD7986 and INS1007). SARS-CoV-2 and COVID-19: CatC has been proposed as a drug target to combat ARDS-associated inflammatory lung damage in patients with severe COVID-19. In this setting CatC inhibitors would be expected to protect the lungs from ARDS by reducing the observed virally-induced hyperinflammation that leads to diffuse alveolar collapse and pulmonary tissue damage [73] ... |
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| RAB27A, member RAS oncogene family (RAB subfamily) |
RAB27A and its effector JFC1 (synaptotagmin like 1) act to regulate neutrophil exocytosis. |
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Small molecule inhibitors of Rab27a-JFC1 binding, termed Nexinhibs (neutrophil exocytosis inhibitors) demonstrate the druggability of Rab GTPases and inhibition of exocytosis of azurophilic granules in human neutrophils without affecting other important innate immune responses, including phagocytosis and neutrophil extracellular trap production. These thus have potential use as an inhibitor of systemic inflammation [62] ... |
| death associated protein kinase 2 (Death-associated kinase (DAPK) family) |
DAPK2 is the prevailing DAPK family member in granulocytes. |
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DAPk2 is recognised as a regulator of apoptosis, autophagy and inflammation [43] ... |
| FGR proto-oncogene, Src family tyrosine kinase (Src family) |
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Fgr may be involved in neutrophil migration, potentially via binding to intergrins [13] ... | |
| HCK proto-oncogene, Src family tyrosine kinase (Src family) |
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Hck is thought to be involved in neutrophil migration, potentially via binding to intergrins [13] ... | |
| LYN proto-oncogene, Src family tyrosine kinase (Src family) |
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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 [39,41,123] ... | |
| elastase, neutrophil expressed (S1: Chymotrypsin) |
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Neutrophil elastase (NE) is a serine proteinase with broad substrate specificity. It is stored in azurophil granules within neutrophils and is involved primarily in host defence. However, in addition to attacking proteins on invading microorganisms, secreted NE also hydrolyzes proteins of the host extracellular matrix, such as collagen-IV and elastin, hence its role in degenerative and inflammatory diseases. NE functions as a promoter of γδ T cell activation via a protease-activated receptor (PAR1)-dependent mechanism [124] ... | |
| proteinase 3 (S1: Chymotrypsin) |
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Proteinase 3 (PR3), called myeloblastin when it was first identified, is an abundant serine protease found principally in neutrophil granules (but is also found on the surface of quiescent human neutrophils from peripheral blood). It is stored in the primary granules of circulating neutrophils alongside other cathepsin C-activated neutrophil serine proteases (NSPs), such as human neutrophil elastase (HNE), CatG, and NSP4. In pathological conditions it is thought that PR3 behaves to accelerate inflammation, by enhancing cytokine bioactivity, inactivating anti-inflammatory mediators and by promoting tissue injury (potentially by degrading extra-cellular matrix components like elastin, collagen, fibronectin, and laminins). In addition, imbalances between NSPs and their endogenous inhibitors can contribute towards pathological tissue damage, such as the damage associated with inflammatory lung diseases like chronic obstructive pulmonary disease (COPD), emphysema, and cystic fibrosis. PR3 inhibitors are considered to be useful clinical candidates for anti-inflammatory drug development [72] ... | |
| mitogen-activated protein kinase kinase kinase kinase 1 (KHS subfamily) |
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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 [51,119] ... | |
| Catalytic Receptors | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| Thymic stromal lymphopoietin receptor (IL-2 receptor family) |
TLSP receptors have been detected on eosiniphils by mRNA expression and flow cytometry. |
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TLSP/TLSPR signalling promotes release of pro-inflammatory Th2 mediators by mast cells and eosinophils [89] ... |
| TLR6 (Toll-like receptor family) |
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TLR6 forms heterodimers with TLR2 to detect a wide range of bacterial lipopeptides (LP) from bacterial cell membranes, and effect an immune response [36] ... | |
| Fc fragment of IgE receptor II (Fc epsilon receptors) |
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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 [66,143] ... | |
| Fc fragment of IgE receptor Ia (Fc epsilon receptors) |
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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. | |
| Other Protein Targets | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| CD300a (CD molecules) |
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CD300a is a member of the CD300 family of leucocyte surface receptors [18] ... | |
| CD33 (Other immune checkpoint proteins, CD33-related SIGLECs, CD molecules) |
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CD33 (SIGLEC3) is a myeloid cell I-type (Ig-type) lectin that binds glycans containing sialic acids [42] ... | |
| leukocyte immunoglobulin like receptor A4 (CD85g) (CD molecules) |
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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) [23] ... | |
| C-type lectin domain family 4 member E (C-type lectin-like receptors (CLRs)) |
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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)) [20] ... | |
| Fc fragment of IgA receptor (Immunoglobulin like domain containing proteins, CD molecules) |
FcαRI (CD89) is constitutively expressed on eosinophils, and neutrophils. |
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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 [85,103] ... |
| CD4 (CD molecules) |
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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 [71,129] ... | |
| sialic acid binding Ig like lectin 8 (CD33-related SIGLECs) |
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SIGLEC8 is a single-pass type I membrane protein. It is a member of the CD33-like subgroup of SIGLECs, and like the other members of this subgroup it carries a conserved cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM) which facilitates its role as an inhibitory receptor on the surface of mast cells and eosinophils [38,65] ... | |
| C-type lectin domain family 12 member A (C-type lectin-like receptors (CLRs)) |
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The CLEC12A protein is a negative regulator of granulocyte and monocyte function [47,86] ... | |
