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Functional and Phenotypic Characterization of Siglec-6 on Human Mast Cells
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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997871/ https://www.ncbi.nlm.nih.gov/pubmed/35406705 http://dx.doi.org/10.3390/cells11071138 |
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author | Robida, Piper A. Rische, Clayton H. Morgenstern, Netali Ben-Baruch Janarthanam, Rethavathi Cao, Yun Krier-Burris, Rebecca A. Korver, Wouter Xu, Alan Luu, Thuy Schanin, Julia Leung, John Rothenberg, Marc E. Wechsler, Joshua B. Youngblood, Bradford A. Bochner, Bruce S. O’Sullivan, Jeremy A. |
author_facet | Robida, Piper A. Rische, Clayton H. Morgenstern, Netali Ben-Baruch Janarthanam, Rethavathi Cao, Yun Krier-Burris, Rebecca A. Korver, Wouter Xu, Alan Luu, Thuy Schanin, Julia Leung, John Rothenberg, Marc E. Wechsler, Joshua B. Youngblood, Bradford A. Bochner, Bruce S. O’Sullivan, Jeremy A. |
author_sort | Robida, Piper A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8997871 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89978712022-04-12 Functional and Phenotypic Characterization of Siglec-6 on Human Mast Cells Robida, Piper A. Rische, Clayton H. Morgenstern, Netali Ben-Baruch Janarthanam, Rethavathi Cao, Yun Krier-Burris, Rebecca A. Korver, Wouter Xu, Alan Luu, Thuy Schanin, Julia Leung, John Rothenberg, Marc E. Wechsler, Joshua B. Youngblood, Bradford A. Bochner, Bruce S. O’Sullivan, Jeremy A. Cells Article 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. MDPI 2022-03-28 /pmc/articles/PMC8997871/ /pubmed/35406705 http://dx.doi.org/10.3390/cells11071138 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Robida, Piper A. Rische, Clayton H. Morgenstern, Netali Ben-Baruch Janarthanam, Rethavathi Cao, Yun Krier-Burris, Rebecca A. Korver, Wouter Xu, Alan Luu, Thuy Schanin, Julia Leung, John Rothenberg, Marc E. Wechsler, Joshua B. Youngblood, Bradford A. Bochner, Bruce S. O’Sullivan, Jeremy A. Functional and Phenotypic Characterization of Siglec-6 on Human Mast Cells |
title | Functional and Phenotypic Characterization of Siglec-6 on Human Mast Cells |
title_full | Functional and Phenotypic Characterization of Siglec-6 on Human Mast Cells |
title_fullStr | Functional and Phenotypic Characterization of Siglec-6 on Human Mast Cells |
title_full_unstemmed | Functional and Phenotypic Characterization of Siglec-6 on Human Mast Cells |
title_short | Functional and Phenotypic Characterization of Siglec-6 on Human Mast Cells |
title_sort | functional and phenotypic characterization of siglec-6 on human mast cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997871/ https://www.ncbi.nlm.nih.gov/pubmed/35406705 http://dx.doi.org/10.3390/cells11071138 |
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