scholarly journals Sphingosine 1-Phosphate-Mediated Trafficking of Pathogenic Th2 and Mast Cells for the Control of Food Allergy

2007 ◽  
Vol 179 (3) ◽  
pp. 1577-1585 ◽  
Author(s):  
Yosuke Kurashima ◽  
Jun Kunisawa ◽  
Morio Higuchi ◽  
Masashi Gohda ◽  
Izumi Ishikawa ◽  
...  
2008 ◽  
Vol 127 ◽  
pp. S34
Author(s):  
Jun Kunisawa ◽  
Yosuke Kurashima ◽  
Morio Higuchi ◽  
Masashi Gohda ◽  
Izumi Ishikawa ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1586
Author(s):  
Tomoe Yashiro ◽  
Hanako Ogata ◽  
Syed Faisal Zaidi ◽  
Jaemin Lee ◽  
Shusaku Hayashi ◽  
...  

Recently, the involvement of the nervous system in the pathology of allergic diseases has attracted increasing interest. However, the precise pathophysiological role of enteric neurons in food allergies has not been elucidated. We report the presence of functional high-affinity IgE receptors (FcεRIs) in enteric neurons. FcεRI immunoreactivities were observed in approximately 70% of cholinergic myenteric neurons from choline acetyltransferase-eGFP mice. Furthermore, stimulation by IgE-antigen elevated intracellular Ca2+ concentration in isolated myenteric neurons from normal mice, suggesting that FcεRIs are capable of activating myenteric neurons. Additionally, the morphological investigation revealed that the majority of mucosal mast cells were in close proximity to enteric nerve fibers in the colonic mucosa of food allergy mice. Next, using a newly developed coculture system of isolated myenteric neurons and mucosal-type bone-marrow-derived mast cells (mBMMCs) with a calcium imaging system, we demonstrated that the stimulation of isolated myenteric neurons by veratridine caused the activation of mBMMCs, which was suppressed by the adenosine A3 receptor antagonist MRE 3008F20. Moreover, the expression of the adenosine A3 receptor gene was detected in mBMMCs. Therefore, in conclusion, it is suggested that, through interaction with mucosal mast cells, IgE-antigen-activated myenteric neurons play a pathological role in further exacerbating the pathology of food allergy.


2019 ◽  
Vol 20 (10) ◽  
pp. 2380 ◽  
Author(s):  
Yu-Ling Chang ◽  
Zhenping Wang ◽  
Satomi Igawa ◽  
Jae Eun Choi ◽  
Tyler Werbel ◽  
...  

Mast cells (MCs) play a significant role in the innate immune defense against bacterial infection through the release of cytokines and antimicrobial peptides. However, their antimicrobial function is still only partially described. We therefore hypothesized that MCs express additional antimicrobial peptides. In this study, we used FANTOM 5 transcriptome data to identify for the first time that MCs express lipocalin 2 (LCN2), a known inhibitor of bacterial growth. Using MCs derived from mice which were deficient in LCN2, we showed that this antimicrobial peptide is an important component of the MCs’ antimicrobial activity against Escherichia coli (E. coli). Since sphingosine-1-phosphate receptors (S1PRs) on MCs are known to regulate their function during infections, we hypothesized that S1P could activate LCN2 production in MCs. Using an in vitro assay, we demonstrated that S1P enhances MCs antimicrobial peptide production and increases the capacity of MCs to directly kill S. aureus and E. coli via an LCN2 release. In conclusion, we showed that LCN2 is expressed by MCs and plays a role in their capacity to inhibit bacterial growth.


2004 ◽  
Vol 24 (19) ◽  
pp. 8765-8777 ◽  
Author(s):  
Nicole Urtz ◽  
Ana Olivera ◽  
Elisa Bofill-Cardona ◽  
Robert Csonga ◽  
Andreas Billich ◽  
...  

ABSTRACT Sphingosine kinase has been recognized as an essential signaling molecule that mediates the intracellular conversion of sphingosine to sphingosine-1-phosphate. In mast cells, induction of sphingosine kinase and generation of sphingosine-1-phosphate have been linked to the initial rise in Ca2+, released from internal stores, and to degranulation. These events either precede or are concomitant with the activation of phospholipase C-γ and the generation of inositol trisphosphate. Here we show that sphingosine kinase type 1 (SPHK1) interacts directly with the tyrosine kinase Lyn and that this interaction leads to the recruitment of this lipid kinase to the high-affinity receptor for immunoglobulin E (FcεRI). The interaction of SPHK1 with Lyn caused enhanced lipid and tyrosine kinase activity. After FcεRI triggering, enhanced sphingosine kinase activity was associated with FcεRI in sphingolipid-enriched rafts of mast cells. Bone marrow-derived mast cells from Lyn−/ − mice, compared to syngeneic wild-type cells, were defective in the initial induction of SPHK1 activity, and the defect was overcome by retroviral Lyn expression. These findings position the activation of SPHK1 as an FcεRI proximal event.


2011 ◽  
Vol 127 (2) ◽  
pp. AB142-AB142
Author(s):  
Y. SONG ◽  
C. Qu ◽  
K.D. Srivastava ◽  
N. Yang ◽  
W. Zhao ◽  
...  

Author(s):  
Aletta D. Kraneveld ◽  
Seil Sagar ◽  
Johan Garssen ◽  
Gert Folkerts

Author(s):  
Yoshihiro Takasato ◽  
Yosuke Kurashima ◽  
Masahiro Kiuchi ◽  
Kiyoshi Hirahara ◽  
Sayuri Murasaki ◽  
...  

AbstractOral immunotherapy (OIT) is an effective approach to controlling food allergy. Although the detailed molecular and cellular mechanisms of OIT are unknown currently, they must be understood to advance the treatment of allergic diseases in general. To elucidate the mechanisms of OIT, especially during the immunological transition from desensitization to allergy regulation, we generated a clinical OIT murine model and used it to examine immunological events of OIT. We found that in mice that completed OIT successfully, desensitized mast cells (MCs) showed functionally beneficial alterations, such as increased induction of regulatory cytokines and enhanced expansion of regulatory T cells. Importantly, these regulatory-T-cell-mediated inhibitions of allergic responses were dramatically decreased in mice lacking OIT-induced desensitized MC. Collectively, these findings show that the desensitization process modulates the activation of MCs, leading directly to enhanced induction of regulatory-T-cell expansion and promotion of clinical allergic unresponsiveness. Our results suggest that efficiently inducing regulatory MCs is a novel strategy for the treatment of allergic disease.


Sign in / Sign up

Export Citation Format

Share Document