IL-33 priming amplifies ATP-mediated mast cell cytokine production

Straus, David B.; Pryor, Destiny T.; Haque, Tamara T.; Kee, Sydney Ann; Dailey, Jordan; Jackson, Kasey L.; Barnstein, Brian; Ryan, John

doi:10.1016/j.cellimm.2021.104470

Cited by 9 publications

(4 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neither the nucleotides (10 -7 -10 -3 M) nor adenosine (10 −6 –10 −3 M) directly triggered degranulation, contrary to results obtained using murine mast cell models ( 129 – 133 ). In HLMC, adenosine exhibited a bimodal effect on anti-IgE-induced histamine release, enhancing it at 10 −6 to 10 −4 M (P > 0.05, NS) and inhibiting it at 10 −3 M (P < 0.05) ( 58 ), in congruence with prior reports on HLMC ( 41 , 134 , 135 ).…”

Section: Introductioncontrasting

confidence: 82%

Degranulation of human mast cells: modulation by P2 receptors’ agonists

Schulman,

Nishi,

Pelleg

2023

Front. Immunol.

View full text Add to dashboard Cite

Since the late 1970s, there has been an alarming increase in the incidence of asthma and its morbidity and mortality. Acute obstruction and inflammation of allergic asthmatic airways are frequently caused by inhalation of exogenous substances such as allergens cross-linking IgE receptors expressed on the surface of the human lung mast cells (HLMC). The degree of constriction of human airways produced by identical amounts of inhaled allergens may vary from day to day and even hour to hour. Endogenous factors in the human mast cell (HMC)’s microenvironment during allergen exposure may markedly modulate the degranulation response. An increase in allergic responsiveness may significantly enhance bronchoconstriction and breathlessness. This review focuses on the role that the ubiquitous endogenous purine nucleotide, extracellular adenosine 5’-triphosphate (ATP), which is a component of the damage-associated molecular patterns, plays in mast cells’ physiology. ATP activates P2 purinergic cell-surface receptors (P2R) to trigger signaling cascades resulting in heightened inflammatory responses. ATP is the most potent enhancer of IgE-mediated HLMC degranulation described to date. Current knowledge of ATP as it relates to targeted receptor(s) on HMC along with most recent studies exploring HMC post-receptor activation pathways are discussed. In addition, the reviewed studies may explain why brief, minimal exposures to allergens (e.g., dust, cat, mouse, and grass) can unpredictably lead to intense clinical reactions. Furthermore, potential therapeutic approaches targeting ATP-related enhancement of allergic reactions are presented.

show abstract

Section: Introductioncontrasting

confidence: 82%

Degranulation of human mast cells: modulation by P2 receptors’ agonists

Schulman,

Nishi,

Pelleg

2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…IL-33 is known to prime variety of cell types to respond more vigorously to external stimuli [ 23 , 24 ]. It has been reported that IL-33 primes mouse MCs with amplified responses to ATP and IgG-mediated activation [ 53 , 54 ]. Our study adds a new IL-33 priming capacity in HSMCs to the existing list.…”

Section: Discussionmentioning

confidence: 99%

IL-33 priming and antigenic stimulation synergistically promote the transcription of proinflammatory cytokine and chemokine genes in human skin mast cells

Gao,

Li,

Guan

et al. 2023

BMC Genomics

View full text Add to dashboard Cite

Background Antigenic stimulation through cross-linking the IgE receptor and epithelial cell-derived cytokine IL-33 are potent stimuli of mast cell (MC) activation. Moreover, IL-33 primes a variety of cell types, including MCs to respond more vigorously to external stimuli. However, target genes induced by the combined IL-33 priming and antigenic stimulation have not been investigated in human skin mast cells (HSMCs) in a genome-wide manner. Furthermore, epigenetic changes induced by the combined IL-33 priming and antigenic stimulation have not been evaluated. Results We found that IL-33 priming of HSMCs enhanced their capacity to promote transcriptional synergy of the IL1B and CXCL8 genes by 16- and 3-fold, respectively, in response to combined IL-33 and antigen stimulation compared to without IL-33 priming. We identified the target genes in IL-33-primed HSMCs in response to the combined IL-33 and antigenic stimulation using RNA sequencing (RNA-seq). We found that the majority of genes synergistically upregulated in the IL-33-primed HSMCs in response to the combined IL-33 and antigenic stimulation were predominantly proinflammatory cytokine and chemokine genes. Moreover, the combined IL-33 priming and antigenic stimulation increase chromatin accessibility in the synergy target genes but not synergistically. Transcription factor binding motif analysis revealed more binding sites for NF-κB, AP-1, GABPA, and RAP1 in the induced or increased chromatin accessible regions of the synergy target genes. Conclusions Our study demonstrates that IL-33 priming greatly potentiates MCs’ ability to transcribe proinflammatory cytokine and chemokine genes in response to antigenic stimulation, shining light on how epithelial cell-derived cytokine IL-33 can cause exacerbation of skin MC-mediated allergic inflammation.

show abstract

“…Although a clear link between MC, IL-33, and ATP in human diseases has not yet been defined, the activation of the TAK1-IKK2-NF-κB pathway is known to play a role in cancer and autoimmune diseases such as psoriasis and rheumatoid arthritis [31], diseases in which MC contribution has been investigated [32][33][34]. Straus et al [35] observed a 3-6-fold increase in the release of IL-6, TNF-α, and IL-13 in response to ATP in BMMCs and peritoneal MCs previously sensitized with IL-33.…”

Section: Introductionmentioning

confidence: 99%

P2X7 Receptor-Induced Human Mast Cell Degranulation Is Enhanced by Interleukin 33

Salcman,

Bahri,

West

et al. 2024

IJMS

View full text Add to dashboard Cite

MCs are tissue-resident immune cells that strategically reside in barrier organs and respond effectively to a wide range of stimuli, such as IL-33, a mediator released upon epithelial damage. Adenosine triphosphate (ATP) accumulates at sites of tissue injury and is known to modulate MC activities. This study investigated how an inflammatory tissue environment rich in IL-33 modulates the ATP-mediated activation of MCs. Human primary MCs primed with IL-33 displayed a strongly increased response to ATP but not ADP. This resulted in increased degranulation, IL-8 release, and pERK1/2 signalling. Such effects are unique to IL-33 stimulation and not shared by the epithelial alarmin, TSLP. MC exposure to IL-33 also increased membrane expression of purinergic and ATP-binding P2X receptors. The use of selective P2X receptor inhibitors identified P2X7 receptor as the key mediator of the enhanced ATP-induced ERK1/2 signalling and degranulation in IL-33-primed MCs. Whilst the inhibition of P2X1 and P2X4 receptors had no effect on MC degranulation, inhibiting these receptors together with P2X7 resulted in further decreased MC-mediated degranulation. These data therefore point toward the potential mechanisms by which IL-33 contributes to the modulation of ATP-mediated activation in human MCs.

show abstract

IL-33 priming amplifies ATP-mediated mast cell cytokine production

Cited by 9 publications

References 40 publications

Degranulation of human mast cells: modulation by P2 receptors’ agonists

Degranulation of human mast cells: modulation by P2 receptors’ agonists

IL-33 priming and antigenic stimulation synergistically promote the transcription of proinflammatory cytokine and chemokine genes in human skin mast cells

P2X7 Receptor-Induced Human Mast Cell Degranulation Is Enhanced by Interleukin 33

Contact Info

Product

Resources

About