IgE and Mast Cells

Oettgen, Hans C.; Burton, Oliver T.

doi:10.1016/bs.ai.2015.03.001

Cited by 20 publications

(8 citation statements)

References 249 publications

(274 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar concerns account for mRNA with reduced expression in SC of MDSC-Exo-treated AA mice. To name a few, reduced recovery of Camp (cationic antimicrobial peptides) ( 102 ), CD55 and Cfb ( 103 ), Chil1 ( 104 ), Clu (clusterin) ( 105 ), F2r (coagulation factor 2) ( 106 ), Fcer1a ( 107 ), Klrk1 ( 108 ), CXCL7 ( 109 ), S100a9 ( 110 ), CD244 ( 111 ), CTSG ( 112 ), Ms4a2 (membrane spanning 4-domains A2) ( 113 ), and VCAM1 ( 114 ) may contribute to impaired activity of the innate immune system and concomitantly dampen adaptive immune system responses. The impact of reduced CD34, Angp1, and Serpinb9 expression remains to be explored.…”

Section: Discussionmentioning

confidence: 99%

Immunoregulatory Effects of Myeloid-Derived Suppressor Cell Exosomes in Mouse Model of Autoimmune Alopecia Areata

et al. 2018

View full text Add to dashboard Cite

The treatment of autoimmune diseases still poses a major challenge, frequently relying on non-specific immunosuppressive drugs. Current efforts aim at reestablishing self tolerance using immune cells with suppressive activity like the regulatory T cells (Treg) or the myeloid-derived suppressor cells (MDSC). We have demonstrated therapeutic efficacy of MDSC in mouse Alopecia Areata (AA). In the same AA model, we now asked whether MDSC exosomes (MDSC-Exo) can replace MDSC. MDSC-Exo from bone marrow cells (BMC) cultures of healthy donors could substantially facilitate treatment. With knowledge on MDSC-Exo being limited, their suitability needs to be verified in advance. Protein marker profiles suggest comparability of BMC- to ex vivo collected inflammatory MDSC/MDSC-Exo in mice with a chronic contact dermatitis, which is a therapeutic option in AA. Proteome analyses substantiated a large overlap of function-relevant molecules in MDSC and MDSC-Exo. Furthermore, MDSC-Exo are taken up by T cells, macrophages, NK, and most avidly by Treg and MDSC-Exo uptake exceeds binding of MDSC themselves. In AA mice, MDSC-Exo preferentially target skin-draining lymph nodes and cells in the vicinity of remnant hair follicles. MDSC-Exo uptake is accompanied by a strong increase in Treg, reduced T helper proliferation, mitigated cytotoxic activity, and a slight increase in lymphocyte apoptosis. Repeated MDSC-Exo application in florid AA prevented progression and sufficed for partial hair regrowth. Deep sequencing of lymphocyte mRNA from these mice revealed a significant increase in immunoregulatory mRNA, including FoxP3 and arginase 1. Downregulated mRNA was preferentially engaged in prohibiting T cell hyperreactivity. Taken together, proteome analysis provided important insights into potential MDSC-Exo activities, these Exo preferentially homing into AA-affected organs. Most importantly, changes in leukocyte mRNA seen after treatment of AA mice with MDSC-Exo sustainably supports the strong impact on the adaptive and the non-adaptive immune system, with Treg expansion being a dominant feature. Thus, MDSC-Exo could potentially serve as therapeutic agents in treating AA and other autoimmune diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Immunoregulatory Effects of Myeloid-Derived Suppressor Cell Exosomes in Mouse Model of Autoimmune Alopecia Areata

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Increased serum IgE levels is one of the characteristic pathology of allergic asthma, which persists for several weeks after the clearance of allergens from the blood [5,6,7,26,27,28]. However, aside from initiating inflammation after allergen crosslinking, there is little evidence in clinical studies that IgE directly contributed to airway wall remodeling.…”

Section: Discussionmentioning

confidence: 99%

IgE Downregulates PTEN through MicroRNA-21-5p and Stimulates Airway Smooth Muscle Cell Remodeling

Fang

Wang

Sun

et al. 2019

IJMS

View full text Add to dashboard Cite

The patho-mechanism leading to airway wall remodeling in allergic asthma is not well understood and remodeling is resistant to therapies. This study assessed the effect of immunoglobulin E (IgE) in the absence of allergens on human primary airway smooth muscle cell (ASMC) remodeling in vitro. ASMCs were obtained from five allergic asthma patients and five controls. Proliferation was determined by direct cell counts, mitochondrial activity by expression of cytochrome c, protein expression by immunoblotting and immuno-fluorescence, cell migration by microscopy imaging, and collagen deposition by cell based ELISA and RNA expression by real time PCR. Non-immune IgE activated two signaling pathways: (i) signal transducer and activator of transcription 3 (STAT3)→miR-21-5p→downregulating phosphatase and tensin homolog (PTEN) expression, and (ii) phosphatidylinositol 3-kinases (PI3K)→protein kinase B (Akt)→mammalian target of rapamycin (mTOR)→ribosomal protein S6 kinase beta-1 (p70s6k)→peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1-α)→peroxisome proliferator-activated receptor-γ (PPAR-γ)→cyclooxygenase-2 (COX-2)→mitochondrial activity, proliferation, migration, and extracellular matrix deposition. Reduced PTEN expression correlated with enhanced PI3K signaling, which upregulated ASMC remodeling. The inhibition of microRNA-21-5p increased PTEN and reduced mTOR signaling and remodeling. Mimics of microRNA-21-5p had opposing effects. IgE induced ASMC remodeling was significantly reduced by inhibition of mTOR or STAT3. In conclusion, non-immune IgE alone is sufficient for stimulated ASMC remodeling by upregulating microRNA-21-5p. Our findings suggest that the suppression of micoRNA-21-5p may present a therapeutic target to reduce airway wall remodeling.

show abstract

“…While the biology of these diseases is complex, all share a central role for mast cell activation as an initiator of symptoms. IgE-mediated mast cell activation elicits release of preformed mediators such as histamine and the production of arachidonic acid metabolites, cytokines, and chemokines that collectively increase vascular permeability, constrict airways, and recruit leukocytes to inflammatory sites (1–3). However, IgE-mediated responses are not exclusively responsible for allergic inflammation.…”

Section: Introductionmentioning

confidence: 99%

TGF-β1 Suppresses IL-33–Induced Mast Cell Function

Ndaw

Abebayehu

Spence

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

TGFβ1 is involved in many pathological conditions, including autoimmune disorders, cancer, cardiovascular and allergic diseases. We have previously found that TGFβ1 can suppress IgE-mediated mast cell activation of human and mouse mast cells. IL-33 is a member of the IL-1 family capable of inducing mast cell responses and enhancing IgE-mediated activation. In this study, we investigated the effects of TGFβ on IL-33-mediated mast cell activation. Bone marrow-derived mast cells cultured in TGFβ −1, −2, or −3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13 and MCP-1, in a concentration-dependent manner. TGFβ1 inhibited IL-33-mediated Akt and ERK phosphorylation as well as NFκB- and AP-1-mediated transcription. These effects were functionally important, as TGFβ1 injection suppressed IL-33-induced systemic cytokines in vivo and inhibited IL-33-mediated cytokine release from human mast cells. TGFβ1 also suppressed the combined effects of IL-33 and IgE-mediated activation on mouse and human mast cells. The role of IL-33 in the pathogenesis of allergic diseases is incompletely understood. These findings, consistent with our previously reported effects of TGFβ1 on IgE-mediated activation, demonstrate that TGFβ1 can provide broad inhibitory signals to activated mast cells.

show abstract

IgE and Mast Cells

Cited by 20 publications

References 249 publications

Immunoregulatory Effects of Myeloid-Derived Suppressor Cell Exosomes in Mouse Model of Autoimmune Alopecia Areata

Immunoregulatory Effects of Myeloid-Derived Suppressor Cell Exosomes in Mouse Model of Autoimmune Alopecia Areata

IgE Downregulates PTEN through MicroRNA-21-5p and Stimulates Airway Smooth Muscle Cell Remodeling

TGF-β1 Suppresses IL-33–Induced Mast Cell Function

Contact Info

Product

Resources

About