Peroxisomes Regulate Cellular Free Fatty Acids to Modulate Mast Cell TLR2, TLR4, and IgE-Mediated Activation
Mast cells are specialized, tissue resident, immune effector cells able to respond to a wide range of stimuli. MCs are involved in the regulation of a variety of physiological functions, including vasodilation, angiogenesis and pathogen elimination. In addition, MCs recruit and regulate the function...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-05-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.856243/full |
| _version_ | 1811345280170196992 |
|---|---|
| author | Dihia Meghnem Dihia Meghnem Dihia Meghnem Edwin Leong Marinella Pinelli Marinella Pinelli Jean S. Marshall Jean S. Marshall Jean S. Marshall Francesca Di Cara Francesca Di Cara |
| author_facet | Dihia Meghnem Dihia Meghnem Dihia Meghnem Edwin Leong Marinella Pinelli Marinella Pinelli Jean S. Marshall Jean S. Marshall Jean S. Marshall Francesca Di Cara Francesca Di Cara |
| author_sort | Dihia Meghnem |
| collection | DOAJ |
| description | Mast cells are specialized, tissue resident, immune effector cells able to respond to a wide range of stimuli. MCs are involved in the regulation of a variety of physiological functions, including vasodilation, angiogenesis and pathogen elimination. In addition, MCs recruit and regulate the functions of many immune cells such as dendritic cells, macrophages, T cells, B cells and eosinophils through their selective production of multiple cytokines and chemokines. MCs generate and release multi-potent molecules, such as histamine, proteases, prostanoids, leukotrienes, heparin, and many cytokines, chemokines, and growth factors through both degranulation dependent and independent pathways. Recent studies suggested that metabolic shifts dictate the activation and granule content secretion by MCs, however the metabolic signaling promoting these events is at its infancy. Lipid metabolism is recognized as a pivotal immunometabolic regulator during immune cell activation. Peroxisomes are organelles found across all eukaryotes, with a pivotal role in lipid metabolism and the detoxification of reactive oxygen species. Peroxisomes are one of the emerging axes in immunometabolism. Here we identified the peroxisome as an essential player in MCs activation. We determined that lack of functional peroxisomes in murine MCs causes a significant reduction of interleukin-6, Tumor necrosis factor and InterleukinL-13 following immunoglobulin IgE-mediated and Toll like receptor 2 and 4 activation compared to the Wild type (WT) BMMCs. We linked these defects in cytokine release to defects in free fatty acids homeostasis. In conclusion, our study identified the importance of peroxisomal fatty acids homeostasis in regulating mast cell-mediated immune functions. |
| first_indexed | 2024-04-13T20:00:47Z |
| format | Article |
| id | doaj.art-f5ef469d0ae24f7aa79ad0de111f7151 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-13T20:00:47Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-f5ef469d0ae24f7aa79ad0de111f71512022-12-22T02:32:13ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-05-011010.3389/fcell.2022.856243856243Peroxisomes Regulate Cellular Free Fatty Acids to Modulate Mast Cell TLR2, TLR4, and IgE-Mediated ActivationDihia Meghnem0Dihia Meghnem1Dihia Meghnem2Edwin Leong3Marinella Pinelli4Marinella Pinelli5Jean S. Marshall6Jean S. Marshall7Jean S. Marshall8Francesca Di Cara9Francesca Di Cara10Dalhousie Human Immunology and Inflammation Group, Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, CanadaDepartment of Pediatrics, Nova Scotia Health Authority IWK, Halifax, NS, CanadaDepartment of Microbiology and Immunology, Dalhousie University, Halifax, NS, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaDepartment of Pediatrics, Nova Scotia Health Authority IWK, Halifax, NS, CanadaDepartment of Microbiology and Immunology, Dalhousie University, Halifax, NS, CanadaDalhousie Human Immunology and Inflammation Group, Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, CanadaDepartment of Microbiology and Immunology, Dalhousie University, Halifax, NS, CanadaDepartment of Pediatrics, Nova Scotia Health Authority IWK, Halifax, NS, CanadaDepartment of Microbiology and Immunology, Dalhousie University, Halifax, NS, CanadaMast cells are specialized, tissue resident, immune effector cells able to respond to a wide range of stimuli. MCs are involved in the regulation of a variety of physiological functions, including vasodilation, angiogenesis and pathogen elimination. In addition, MCs recruit and regulate the functions of many immune cells such as dendritic cells, macrophages, T cells, B cells and eosinophils through their selective production of multiple cytokines and chemokines. MCs generate and release multi-potent molecules, such as histamine, proteases, prostanoids, leukotrienes, heparin, and many cytokines, chemokines, and growth factors through both degranulation dependent and independent pathways. Recent studies suggested that metabolic shifts dictate the activation and granule content secretion by MCs, however the metabolic signaling promoting these events is at its infancy. Lipid metabolism is recognized as a pivotal immunometabolic regulator during immune cell activation. Peroxisomes are organelles found across all eukaryotes, with a pivotal role in lipid metabolism and the detoxification of reactive oxygen species. Peroxisomes are one of the emerging axes in immunometabolism. Here we identified the peroxisome as an essential player in MCs activation. We determined that lack of functional peroxisomes in murine MCs causes a significant reduction of interleukin-6, Tumor necrosis factor and InterleukinL-13 following immunoglobulin IgE-mediated and Toll like receptor 2 and 4 activation compared to the Wild type (WT) BMMCs. We linked these defects in cytokine release to defects in free fatty acids homeostasis. In conclusion, our study identified the importance of peroxisomal fatty acids homeostasis in regulating mast cell-mediated immune functions.https://www.frontiersin.org/articles/10.3389/fcell.2022.856243/fullperoxisomemast cellIgETLRfree fatty acids |
| spellingShingle | Dihia Meghnem Dihia Meghnem Dihia Meghnem Edwin Leong Marinella Pinelli Marinella Pinelli Jean S. Marshall Jean S. Marshall Jean S. Marshall Francesca Di Cara Francesca Di Cara Peroxisomes Regulate Cellular Free Fatty Acids to Modulate Mast Cell TLR2, TLR4, and IgE-Mediated Activation Frontiers in Cell and Developmental Biology peroxisome mast cell IgE TLR free fatty acids |
| title | Peroxisomes Regulate Cellular Free Fatty Acids to Modulate Mast Cell TLR2, TLR4, and IgE-Mediated Activation |
| title_full | Peroxisomes Regulate Cellular Free Fatty Acids to Modulate Mast Cell TLR2, TLR4, and IgE-Mediated Activation |
| title_fullStr | Peroxisomes Regulate Cellular Free Fatty Acids to Modulate Mast Cell TLR2, TLR4, and IgE-Mediated Activation |
| title_full_unstemmed | Peroxisomes Regulate Cellular Free Fatty Acids to Modulate Mast Cell TLR2, TLR4, and IgE-Mediated Activation |
| title_short | Peroxisomes Regulate Cellular Free Fatty Acids to Modulate Mast Cell TLR2, TLR4, and IgE-Mediated Activation |
| title_sort | peroxisomes regulate cellular free fatty acids to modulate mast cell tlr2 tlr4 and ige mediated activation |
| topic | peroxisome mast cell IgE TLR free fatty acids |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.856243/full |
| work_keys_str_mv | AT dihiameghnem peroxisomesregulatecellularfreefattyacidstomodulatemastcelltlr2tlr4andigemediatedactivation AT dihiameghnem peroxisomesregulatecellularfreefattyacidstomodulatemastcelltlr2tlr4andigemediatedactivation AT dihiameghnem peroxisomesregulatecellularfreefattyacidstomodulatemastcelltlr2tlr4andigemediatedactivation AT edwinleong peroxisomesregulatecellularfreefattyacidstomodulatemastcelltlr2tlr4andigemediatedactivation AT marinellapinelli peroxisomesregulatecellularfreefattyacidstomodulatemastcelltlr2tlr4andigemediatedactivation AT marinellapinelli peroxisomesregulatecellularfreefattyacidstomodulatemastcelltlr2tlr4andigemediatedactivation AT jeansmarshall peroxisomesregulatecellularfreefattyacidstomodulatemastcelltlr2tlr4andigemediatedactivation AT jeansmarshall peroxisomesregulatecellularfreefattyacidstomodulatemastcelltlr2tlr4andigemediatedactivation AT jeansmarshall peroxisomesregulatecellularfreefattyacidstomodulatemastcelltlr2tlr4andigemediatedactivation AT francescadicara peroxisomesregulatecellularfreefattyacidstomodulatemastcelltlr2tlr4andigemediatedactivation AT francescadicara peroxisomesregulatecellularfreefattyacidstomodulatemastcelltlr2tlr4andigemediatedactivation |