IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10–Deficient Mice

Polukort, Stephanie; Rovatti, Jeffrey; Carlson, Logan; Thompson, C. R.; Ser‐Dolansky, Jennifer; Kinney, Shannon R. Morey; Schneider, Sallie S.; Mathias, Clinton B.

doi:10.4049/jimmunol.1600066

Cited by 68 publications

(99 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, uninfected IL‐10 deficient mice exhibited less of a temperature drop after systemic allergen challenge (Figure B) than uninfected wild‐type mice (Figure C). This is consistent with two recent studies, one showing that IL‐10 can potentially enhance IgE‐mediated mast cell function and another demonstrating that the absence of IL‐10 is associated with reduced disease in a murine food allergy model . As we did not evaluate uninfected IL‐10 deficient and wild‐type mice in the same experimental trials, definitive determination of whether IL‐10 enhances systemic anaphylaxis will be a focus of future studies.…”

Section: Discussionsupporting

confidence: 90%

“…Finally, we also investigated the requirement of IL‐10 in conferring protection against anaphylaxis. IL‐10 has been implicated as having both enhancing and suppressive effects on IgE‐mediated inflammation . Previously, our laboratory found that host IL‐10 production is responsible for helminth‐mediated suppression of basophil sensitivity to IgE‐mediated activation .…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Chronic infection with a tissue‐invasive helminth attenuates sublethal anaphylaxis and reduces granularity and number of mast cells

Kropp

Jackson-Thompson

Thomas

et al. 2020

Clin Experimental Allergy

View full text Add to dashboard Cite

Background: Immunoglobulin E (IgE)-mediated anaphylaxis is a potentially fatal condition in which allergy effector cells rapidly discharge pre-formed inflammatory mediators. Treatments that address the immune component of allergic anaphylaxis are inadequate. Helminths have been previously shown to suppress effector cell function; however, their ability to treat pre-existing allergy remains unclear.Objective: To evaluate the ability of chronic helminth infection to protect against anaphylaxis in previously sensitized mice.Methods: A sublethal model of anaphylaxis was used, in which BALB/c mice were sensitized by three intraperitoneal (i.p.) injections of OVA/alum. Temperature drop was then monitored after systemic OVA challenge in uninfected mice and in mice infected chronically with Litomosoides sigmodontis, a tissue-invasive filarial nematode. Results:Litomosoides sigmodontis-infected mice exhibited significantly lower serum levels of mMCP-1 and were less hypothermic at 30-minute post-challenge compared to uninfected OVA-challenged controls. Characterization of anaphylaxis revealed that FcԑR1 and mast cells were required for hypothermia and elevated serum mMCP-1.OVA-IgE and OVA-IgG1 serum levels were not significantly altered by L sigmodontis infection, and experiments with IL-10 −/− mice demonstrated that IL-10 was not required for protection against anaphylaxis. However, peritoneal mast cell numbers were significantly lower in infected mice, and those that were present exhibited decreased granularity by flow cytometry and marked depletion of intracytoplasmic granules by light microscopy. Mast cells from infected mice had lower expression of the activation markers CD200R and CD63 and contained significantly lower basal stores of histamine. Conclusions:Chronic L sigmodontis infection protects against anaphylaxis, likely due to reduction in mast cell numbers and depletion of pre-formed inflammatory mediators in remaining mast cells. K E Y W O R D Sallergy, anaphylaxis, helminth, immunoglobulin E, mast cells, parasites

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 95%

Chronic infection with a tissue‐invasive helminth attenuates sublethal anaphylaxis and reduces granularity and number of mast cells

Kropp

Jackson-Thompson

Thomas

et al. 2020

Clin Experimental Allergy

View full text Add to dashboard Cite

show abstract

“…In contrast to our observations, recent reports indicate that IL‐10 can enhance IgE‐mediated MC responses in vivo . However, the requirement of IL‐10 in the induction of IgE‐MC–dependent food allergic response appeared to be related to the capability of IL‐10 to alter MC proliferation and numbers . Previous studies by us and others have reported a requirement for small intestine (SI) MC expansion in IgE‐mediated, MC‐dependent food allergic responses in mice.…”

Section: Discussioncontrasting

confidence: 99%

“…can enhance IgE-mediated MC responses in vivo. 64 However, the requirement of IL-10 in the induction of IgE-MC-dependent food allergic response appeared to be related to the capability of IL-10 to alter MC proliferation and numbers. 64 60,62 It is possible that a combinatory effect of decreased surface expression of FceRI and reduced IgE-FceRI signalling machinery may be required to drive the lack of responsiveness to IgE.…”

Section: Mcs Express Tlr Receptors Including Tlr-4 and Expression Andmentioning

confidence: 99%

Lipopolysaccharide suppresses IgE‐mast cell‐mediated reactions

Wang

McKell

Dang

et al. 2017

Clin Experimental Allergy

View full text Add to dashboard Cite

Background Clinical and experimental analyses have identified a central role for IgE/FcεRI/mast cells in promoting IgE-mediated anaphylaxis. Recent data from human studies suggest that bacterial infections can alter susceptibility to anaphylaxis. Objective We examined the effect of LPS exposure on the induction of IgE-mast cell-(MC) mediated reactions in mice. Methods C57BL/6 WT, TLR-4−/− and IL10−/− mice were exposed to LPS and serum cytokines (TNF and IL-10) were measured. Mice were subsequently treated with anti-IgE and the symptoms of passive IgE-mediated anaphylaxis, MC activation, Ca2+-mobilization and expression of FcεRI on peritoneal MCs were quantitated. Results We show that LPS exposure of C57BL/6 WT mice constrains IgE-MC mediated reactions. LPS-induced suppression of IgE-MC mediated responses was TLR-4-dependent and associated with increased systemic IL-10 levels, decreased surface expression of FcεRI on MCs and loss of sensitivity to IgE activation. Notably, LPS-induced desensitization of MCs was short-term with MC sensitivity to IgE reconstituted within 48 hours which was associated with recapitulation of FcεRI expression on the MCs. Mechanistic analyses revealed a requirement for IL-10 in LPS-mediated decrease in MC FcεRI surface expression. Conclusions & Clinical Relevance Collectively, these studies suggest that LPS-induced IL-10 promotes the down regulation of MC surface FcεRI expression and leads to desensitization of mice to IgE-mediated reactions. These studies indicate that targeting of the LPS-TLR-4-IL-10-pathway maybe used as a therapeutic approach to prevent adverse IgE-mediated reactions.

show abstract

“…149 The latter study reported IL10 upregulation as a potential mechanism for immunomodulation of the tumor microenvironment. This is especially interesting in light of recent studies from hypersensitivity research demonstrating that IL10 has pro-T H 2 inflammatory effects, 150,151 which are in contrast to IL10 being thought of as an immunosuppressive cytokine. Could IL10 application be utilized to enhance antitumor immune-system responses, specifically T-cell and innate lymphoid-cell programming?…”

Section: Cytokinesmentioning

confidence: 99%

Current insights into matrix metalloproteinases and glioma progression: transcending the degradation boundary

Pullen¹,

Pickford²,

Perry³

et al. 2018

MNM

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) remains one of the most deadly cancers, with modest advances in overall survival despite significant improvements in imaging, surgery, and molecular genomic understanding. The highest-grade glioma, GBM is a primary brain cancer that is molecularly heterogeneous among patients and even within the same patient. Key hallmarks include glioma-cell invasion, angiogenesis, and therapeutic resistance. While once considered a major player in glioma invasion, members of the MMP family are also associated with other key pathological hallmarks of glioma. Investigations into understanding MMP function in GBM were slowed due to the failed MMP-inhibitor trials for GBM in the 2000s. In contrast, the field of MMPs in other brain pathologies has flourished in such areas as traumatic brain injury, multiple sclerosis, and stroke. In the past decade, the increase in publicly available data sets documenting patient-biopsy molecular information has empowered laboratory investigations into the spectrum of genomic, transcriptomic, and proteomic changes associated with glioma, including MMPs. In this review, we selected one of these data sets to illustrate a small sample of information that can be obtained from such analyses. Combined with recent reports on the use of MMP-cleavable peptides for imaging and the multifunctionality of MMPs, including intracellular nonproteolytic actions in various cell types, this paves the way for new avenues of MMP research. Understanding the function of MMPs in host-tumor interactions both spatially and temporally during tumor progression and in response to treatment will be crucial for the advancement of targeting specific MMPs in GBM. The opportunities to explore MMP regulation, expression, and function further in GBM have never been so great with progress in modern bioinformatics and molecular techniques, and it is hoped that advancements will translate in some way to patients diagnosed with GBM.

show abstract

IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10–Deficient Mice

Cited by 68 publications

References 55 publications

Chronic infection with a tissue‐invasive helminth attenuates sublethal anaphylaxis and reduces granularity and number of mast cells

Chronic infection with a tissue‐invasive helminth attenuates sublethal anaphylaxis and reduces granularity and number of mast cells

Lipopolysaccharide suppresses IgE‐mast cell‐mediated reactions

Current insights into matrix metalloproteinases and glioma progression: transcending the degradation boundary

Contact Info

Product

Resources

About