Targets Associated to Immuno Cell Types - Mast cells
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The Mast cells 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) |
In humans, mast cells express H1R, H2R and H4R. |
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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) |
In humans, mast cells express H1R, H2R and H4R. |
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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 [110] ... |
| H4 receptor (Histamine receptors) |
In humans, mast cells express H1R, H2R and H4R. |
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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 [103,166] ... |
| H3 receptor (Histamine receptors) |
In humans, H3R expression is restricted to brain mast cells. |
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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. |
| CCR3 (Chemokine receptors) |
CCR3 is expressed on mast cells, basophils, 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) |
Cord blood mast cells express S1P1R and S1P2R |
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S1P1R activation by agonists downregulates allergic inflammation (i.e. it has an inhibitory effect) [60-61,124] ... |
| S1P2 receptor (Lysophospholipid (S1P) receptors) |
Cord blood mast cells express S1P1R and S1P2R |
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Activation of S1P2R has pro-inflammatory effects (e.g. mast cell degranulation, regulation of pro-inflammatory cytokine production, and cytokine and chemokine release [74,107] ... |
| CB2 receptor (Cannabinoid receptors) |
Mast cells express both cannabinoid receptors. |
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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 [105] ... |
| CB1 receptor (Cannabinoid receptors) |
Mast cells express both cannabinoid receptors, although the CB1 receptor is most abundantly expressed in the central nervous system. |
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CB1 receptor is involved in controlling mast cell degranulation and maturation [137] ... |
| MRGPRX2 (Class A Orphans) |
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Expression of MRGPRX2 was initially reported predominantly in sensory neurons of the dorsal root ganglion. More recently expression has been detected in human mast cells. In these cells the receptor is activated by the antimicrobial peptide LL-37, resulting in calcium mobilisation and degranulation [95,136] ... | |
| 5-HT1A receptor (5-Hydroxytryptamine receptors) |
Involved in mast cell chemotaxix. |
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The chemoattractant properties of 5-HT on both human and mouse mast cells are mediated by 5-HT1A receptor [76] ... |
| C3a receptor (Complement peptide receptors) |
C3aR expression was not detected in mouse mast cells using a floxed tdTomato-C3aR reporter knock-in system (Quell et al., 2017). |
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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 [139,154] ... |
| A2A receptor (Adenosine receptors) |
A2A receptor is expressed by LAD2 mast cells at the mRNA and protein levels. Flow cytometry of permeabilised cells detected receptor protein in intracellular pools. By mRNA expression level, the A2A receptor was the most abundantly expressed of the four adenosine receptor subtypes (A2A > A2B > A3; A1 mRNA not detected). |
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Agonist stimulation of the A2A and A3 receptors down-regulates production of the pro-inflammatory mediators TNF-α and IL-8 in human synoviocytes [148] ... |
| A2B receptor (Adenosine receptors) |
A2B receptor is expressed by LAD2 mast cells at the mRNA and protein levels. Flow cytometry of permeabilised cells detected receptor protein in intracellular pools. By mRNA expression level, the A2A receptor was the most abundantly expressed of the four adenosine receptor subtypes (A2A > A2B > A3; A1 mRNA not detected). |
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A2B receptor is discussed in this immuno-oncology review [2] ... |
| CCR4 (Chemokine receptors) |
CCR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. In disease states CCR4 is involved in recruiting T helper type 2 cell (Th2) subsets in autoimmune disorders such as asthma, allergic rhinitis, and atopic dermatitis [133] ... |
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| β2-adrenoceptor (Adrenoceptors) |
Mast cell histamine release was increased in coculture with human airways smooth muscle cells and this was enhanced by β2-AR agonists. Inhibition of mast cell mediator release by β2-AR-agonists was reduced in coculture. β2-AR agonists did not prevent smooth muscle cell contraction when mast cells were present, but this was reversed by corticosteroids. |
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β2-ARs are expressed on innate and adaptive immune cells of humans and rodents, and are reported to have an immuno-modulating effect [31] ... |
| Ion Channels | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| TRPA1 (Transient Receptor Potential channels (TRP)) |
TRPA1 is reported to be involved mast cell secretory granule formation in rat. | Several lines of evidence implicate TRPA1 in inflammation, inflammatory pain and inflammatory diseases [75,89,97,111,135,169] ... | |
| KCa3.1 (Calcium- and sodium-activated potassium channels (KCa, KNa)) |
KCa3.1 is expressed by mast cells. | 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 [29,36,92] ... | |
| Orai1 (Orai channels) |
Orai1 on mast cells is involved in their degranulation, histamine release and cytokine production and in the immediate dermal response to an allergen-IgE interaction (a.k.a. passive cutaneous anaphylaxis). |
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ORAI1 is the gene that encodes the essential pore-forming subunit of CRAC store-operated Ca2+ entry (SOCE) channels [113] ... |
| P2X1 (P2X receptors) |
P2XR1 and P2XR3 are expressed by mast cells. |
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Functional P2X1 receptors are expressed by healthy human eosinophils [159] ... |
| P2X3 (P2X receptors) |
P2XR1 and P2XR3 are expressed by mast cells. |
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P2X ligand-gated ion channels elicit pro-inflammatory immune responses upon activation by extracellular ATP that acts as a DAMP when released from damaged or infected cells [19,22] ... |
| TRPM4 (Transient Receptor Potential channels (TRP)) |
TRPM4 is involved in mast cell function. |
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TRPM4 is expressed on human T cells, mouse dendritic cells, human and mouse monocytes/macrophages, and mouse mast cells [109] ... |
| TRPV2 (Transient Receptor Potential channels (TRP)) |
Expressed on human, mouse and rat mast cells. | Expressed on human and mouse B cells, human dendritic cells and neutrophils, mouse monocytes/macrophages, and human, mouse and rat mast cells [109] ... | |
| Enzymes | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| cathepsin C (C1: Papain) |
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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| PLCγ1 (Phosphoinositide-specific phospholipase C) |
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Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [47,121] ... | |
| PLCγ2 (Phosphoinositide-specific phospholipase C) |
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Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [47,121] ... | |
| SRC proto-oncogene, non-receptor tyrosine kinase (Src family) |
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Src family tyrosine kinases act as general modulators of immune cell signaling, playing diverse signaling functions, both inhibitory and stimulatory, in immunoreceptor and integrin signaling pathways [88] ... | |
| FYN proto-oncogene, Src family tyrosine kinase (Src family) |
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Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [108] ... | |
| 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 [38,44,146] ... | |
| FER tyrosine kinase (Fer family) |
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FER acts downstream of the activated high affinity immunoglobulin epsilon receptor (FCεR1) and plays a role in FCεR1-mediated signaling in mast cells, regulation of mast cell degranulation, leukocyte recruitment, and leukocyte extravasation following bacterial lipopolysaccharide (LPS ... | |
| chymase 1 (S1: Chymotrypsin) |
Chymase is present in mast cell secretory granules. |
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Chymase is a chymotrypsin-like serine protease that is expressed by mast cells. Amongst its activities, chymase is involved in the conversion of angiotensin (AT) I to ATII, its protease activity cleaves latent TGFβ1 and IL-1β in the cellular environment to generate the active cytokines, and it can further stimulate mast cell degranulation in a self-amplification loop. The potential of chymase as a drug target for inflammatory and gastrointestinal disorders is reviewed by Heuston and Hyland (2012) [54] ... |
| 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 [53,132] ... | |
| protein kinase C theta (Delta subfamily) |
PKC-θ is a novel subfamily PKC found predominantly in hematopoietic cells [11] ... | ||
| Catalytic Receptors | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| KIT proto-oncogene, receptor tyrosine kinase (Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family) |
Mast cells ubiquitously express KIT. It is expressed by mast cell precursors and mature mast cells. |
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Stem cell factor (SCF) and its receptor KIT (c-KIT) play an essential part in mast cell biology. In addition to CSF/KIT-mediated regulation of mast cell development, proliferation and survival, KIT is also reported to be involved in the adhesion of mast cells to human airway epithelial cells (a homing and adhesion role), suggesting a mechanism that could be targeted for anti-asthmatic potential [48] ... |
| Interleukin-1 receptor-like 1 (Immunoglobulin-like family of IL-1 receptors) |
IL1RL1 (ST2) is the ligand binding subunit of the functional receptor for IL-33. It is mainly expressed on mast cells, eosinophils and other immune cells [43] ... | ||
| Thymic stromal lymphopoietin receptor (IL-2 receptor family) |
Functional TLSP receptors are reported on the surface of mast cells. |
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TLSP/TLSPR signalling promotes release of pro-inflammatory Th2 mediators by mast cells and eosinophils [98] ... |
| Fc fragment of IgE receptor Ia (Fc epsilon receptors) |
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. | ||
| Transporters | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| Vesicular polyamine transporter (SLC18 family of vesicular amine transporters) |
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VPAT is expressed by mast cells and is responsible for vesicular storage of the polyamines, spermine and spermidine, in granules distinct from those containing histamine or serotonin [141] ... | |
| Other Protein Targets | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| CD300a (CD molecules) |
Functional CD300a is expressed on human mast cells. |
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CD300a is a member of the CD300 family of leucocyte surface receptors [17] ... |
| regulator of G-protein signaling 13 (R4 family) |
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RGS13 is involved in a range of immune system and inflammatory processes [90,129,138] ... | |
| 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 [37,69] ... | |
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