Biomaterial Database

Functional and Phenotypic Characterization of Siglec-6 on Human Mast Cells. 2022

Piper A Robida, and Clayton H Rische, and Netali Ben-Baruch Morgenstern, and Rethavathi Janarthanam, and Yun Cao, and Rebecca A Krier-Burris, and Wouter Korver, and Alan Xu, and Thuy Luu, and Julia Schanin, and John Leung, and Marc E Rothenberg, and Joshua B Wechsler, and Bradford A Youngblood, and Bruce S Bochner, and Jeremy A O'Sullivan

Division of Allergy and Immunology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Mast cells are tissue-resident cells that contribute to allergic diseases, among others, due to excessive or inappropriate cellular activation and degranulation. Therapeutic approaches to modulate mast cell activation are urgently needed. Siglec-6 is an immunoreceptor tyrosine-based inhibitory motif (ITIM)-bearing receptor selectively expressed by mast cells, making it a promising target for therapeutic intervention. However, the effects of its engagement on mast cells are poorly defined. Siglec-6 expression and endocytosis on primary human mast cells and mast cell lines were assessed by flow cytometry. SIGLEC6 mRNA expression was examined by single-cell RNAseq in esophageal tissue biopsy samples. The ability of Siglec-6 engagement or co-engagement to prevent primary mast cell activation was determined based on assessments of mediator and cytokine secretion and degranulation markers. Siglec-6 was highly expressed by all mast cells examined, and the SIGLEC6 transcript was restricted to mast cells in esophageal biopsy samples. Siglec-6 endocytosis occurred with delayed kinetics relative to the related receptor Siglec-8. Co-crosslinking of Siglec-6 with FcεRIα enhanced the inhibition of mast cell activation and diminished downstream ERK1/2 and p38 phosphorylation. The selective, stable expression and potent inhibitory capacity of Siglec-6 on human mast cells are favorable for its use as a therapeutic target in mast cell-driven diseases.

UI	MeSH Term	Description	Entries
D008407	Mast Cells	Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the BASOPHILS, mast cells contain large amounts of HISTAMINE and HEPARIN. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the STEM CELL FACTOR.	Basophils, Tissue,Basophil, Tissue,Cell, Mast,Cells, Mast,Mast Cell,Tissue Basophil,Tissue Basophils
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015214	Antigens, Differentiation, Myelomonocytic	Surface antigens expressed on myeloid cells of the granulocyte-monocyte-histiocyte series during differentiation. Analysis of their reactivity in normal and malignant myelomonocytic cells is useful in identifying and classifying human leukemias and lymphomas.	Differentiation Antigens, Myelomonocytic,Myelomonocytic Differentiation Antigens,Antigens, Myelomonocytic, Differentiation,Antigens, Myelomonocytic Differentiation
D015703	Antigens, CD	Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.	CD Antigen,Cluster of Differentiation Antigen,Cluster of Differentiation Marker,Differentiation Antigens, Leukocyte, Human,Leukocyte Differentiation Antigens, Human,Cluster of Differentiation Antigens,Cluster of Differentiation Markers,Antigen Cluster, Differentiation,Antigen, CD,CD Antigens,Differentiation Antigen Cluster,Differentiation Marker Cluster,Marker Cluster, Differentiation
D037102	Lectins	Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.	Animal Lectin,Animal Lectins,Isolectins,Lectin,Isolectin,Lectin, Animal,Lectins, Animal
D063265	Sialic Acid Binding Immunoglobulin-like Lectins	A family of SIALIC ACID binding proteins found in vertebrate species. They are transmembrane proteins which act as cell surface receptors for a variety of sialylated GLYCOCONJUGATES. While a subset of siglec protein subtypes are evolutionarily conserved between mammalian species, there are many others that are species specific.	Sialic Acid Binding Ig-like Lectin,Sialic Acid-binding Hemagglutinin,Siglec,Siglecs,Hemagglutinin, Sialic Acid-binding,Sialic Acid Binding Ig like Lectin,Sialic Acid Binding Immunoglobulin like Lectins,Sialic Acid binding Hemagglutinin