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Divergent Effects of Acute and Prolonged Interleukin 33 Exposure on Mast Cell IgE-Mediated Functions

Rönnberg, Elin (author)
Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Immunol & Allergy Unit, Solna, Sweden
Ghaib, Avan (author)
Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Immunol & Allergy Unit, Solna, Sweden;Univ Sulaimani, Coll Med, Dept Microbiol, Sulaimani, Iraq
Ceriol, Carlos (author)
Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Immunol & Allergy Unit, Solna, Sweden
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Enoksson, Mattias (author)
Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Immunol & Allergy Unit, Solna, Sweden
Arock, Michel (author)
CNRS, UMR 8113, Ecole Normale Super Cachan, Mol & Cellular Oncol,LBPA, Cachan, France;Grp Hosp Pitie Salpetriere, Lab Cent Hematol, Paris, France
Säfholm, Jesper (author)
Karolinska Institutet,Karolinska Inst, Inst Environm Med, Unit Asthma & Allergy Res, Solna, Sweden
Orre, Ann-Charlotte (author)
Al-Ameri, Mamdoh (author)
Karolinska Institutet
Adner, Mikael (author)
Karolinska Institutet
Dahlen, Sven-Erik (author)
Karolinska Institutet
Ekoff, Maria (author)
Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Immunol & Allergy Unit, Solna, Sweden
Nilsson, Gunnar (author)
Uppsala universitet,Hematologi,Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Immunol & Allergy Unit, Solna, Sweden
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 (creator_code:org_t)
2019-06-19
2019
English.
In: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 10
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Background: Epithelial cytokines, including IL-33 and Thymic stromal lymphopoietin (TSLP), have attracted interest because of their roles in chronic allergic inflammation-related conditions such as asthma. Mast cells are one of the major targets of IL-33, to which they respond by secreting cytokines. Most studies performed thus far have investigated the acute effects of IL-33 on mast cells. In the current study, we investigated how acute vs. prolonged exposure of mast cells to IL-33 and TSLP affects mediator synthesis and IgE-mediated activation.Methods: Human lung mast cells (HLMCs), cord blood-derived mast cells (CBMCs), and the ROSA mast cell line were used for this study. Receptor expression and the levels of mediators were measured after treatment with IL-33 and/or TSLP.Results: IL-33 induced the release of cytokines. Prolonged exposure to IL-33 increased while TSLP reduced intracellular levels of tryptase. Acute IL-33 treatment strongly potentiated IgE-mediated activation. In contrast, 4 days of exposure to IL-33 decreased IgE-mediated activation, an effect that was accompanied by a reduction in Fc epsilon RI expression.Conclusion: We show that IL-33 plays dual roles in mast cells, in which its acute effects include cytokine release and the potentiation of IgE-mediated degranulation, whereas prolonged exposure to IL-33 reduces IgE-mediated activation. We conclude that mast cells act quickly in response to the alarmin IL-33 to initiate an acute inflammatory response, whereas extended exposure to IL-33 during prolonged inflammation reduces IgE-mediated responses. This negative feedback effect suggests the presence of a novel regulatory pathway that modulates IgE-mediated human mast cell responses.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Keyword

Fc epsilon RI
IgE
IL-33
mast cells
TSLP

Publication and Content Type

ref (subject category)
art (subject category)

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