Interleukin-33 amplifies human mast cell activities induced by complement anaphylatoxinsCitation formats

  • External authors:
  • Rajia Bahri
  • Karen Garcia Rodriguez
  • Georgia Sweetland
  • Georgia Wileman
  • Rajesh Shah
  • Angeles Montero-Fernandez
  • Laura Rapley

Standard

Interleukin-33 amplifies human mast cell activities induced by complement anaphylatoxins. / West, Peter; Bahri, Rajia; Garcia Rodriguez, Karen; Sweetland, Georgia; Wileman, Georgia; Shah, Rajesh; Montero-Fernandez, Angeles; Rapley, Laura; Bulfone-Paus, Silvia.

In: Frontiers in Immunology, 11.12.2020.

Research output: Contribution to journalArticlepeer-review

Harvard

West, P, Bahri, R, Garcia Rodriguez, K, Sweetland, G, Wileman, G, Shah, R, Montero-Fernandez, A, Rapley, L & Bulfone-Paus, S 2020, 'Interleukin-33 amplifies human mast cell activities induced by complement anaphylatoxins', Frontiers in Immunology.

APA

West, P., Bahri, R., Garcia Rodriguez, K., Sweetland, G., Wileman, G., Shah, R., Montero-Fernandez, A., Rapley, L., & Bulfone-Paus, S. (Accepted/In press). Interleukin-33 amplifies human mast cell activities induced by complement anaphylatoxins. Frontiers in Immunology.

Vancouver

West P, Bahri R, Garcia Rodriguez K, Sweetland G, Wileman G, Shah R et al. Interleukin-33 amplifies human mast cell activities induced by complement anaphylatoxins. Frontiers in Immunology. 2020 Dec 11.

Author

West, Peter ; Bahri, Rajia ; Garcia Rodriguez, Karen ; Sweetland, Georgia ; Wileman, Georgia ; Shah, Rajesh ; Montero-Fernandez, Angeles ; Rapley, Laura ; Bulfone-Paus, Silvia. / Interleukin-33 amplifies human mast cell activities induced by complement anaphylatoxins. In: Frontiers in Immunology. 2020.

Bibtex

@article{07e572306b524ddbba27a0a12e966fbf,
title = "Interleukin-33 amplifies human mast cell activities induced by complement anaphylatoxins",
abstract = "Both, aberrant mast cell responses and complement activation contribute to allergic diseases. Since mast cells are highly responsive to C3a and C5a, while Interleukin-33 (IL-33) is a potent mast cell activator, we hypothesized that IL-33 critically regulates mast cell responses to complement anaphylatoxins. We sought to understand whether C3a and C5a differentially activate primary human mast cells, and probe whether IL-33 regulates C3a/C5a-induced mast cell activities. Primary human mast cells were generated from peripheral blood precursors or isolated from healthy human lung tissue, and mast cell complement receptor expression, degranulation, mediator release, phosphorylation patterns, and calcium flux were assessed. Human mast cells of distinct origin express constitutively higher levels of C3aR1 than C5aR1, and both receptors are downregulated by anaphylatoxins. While C3a is a potent mast cell degranulation inducer, C5a is a weaker secretagogue with more delayed effects. Importantly, IL-33 potently enhances the human mast cell reactivity to C3a and C5a (degranulation, cytokine and chemokine release), independent of changes in C3a or C5a receptor expression or the level of Ca2+ influx. Instead, this reflects differential dynamics of intracellular signaling such as ERK1/2 phosphorylation. Since primary human mast cells respond differentially to anaphylatoxin stimulation, and that IL-33 is a key regulator of mast cell responses to complement anaphylatoxins, this is likely to aggravate Th2 immune responses. This newly identified cross-regulation may be important for controlling exacerbated complement- and mast cell-dependent Th2 responses and thus provides an additional rationale for targeting anti-IL33 therapeutically in allergic diseases.",
author = "Peter West and Rajia Bahri and {Garcia Rodriguez}, Karen and Georgia Sweetland and Georgia Wileman and Rajesh Shah and Angeles Montero-Fernandez and Laura Rapley and Silvia Bulfone-Paus",
year = "2020",
month = dec,
day = "11",
language = "English",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",

}

RIS

TY - JOUR

T1 - Interleukin-33 amplifies human mast cell activities induced by complement anaphylatoxins

AU - West, Peter

AU - Bahri, Rajia

AU - Garcia Rodriguez, Karen

AU - Sweetland, Georgia

AU - Wileman, Georgia

AU - Shah, Rajesh

AU - Montero-Fernandez, Angeles

AU - Rapley, Laura

AU - Bulfone-Paus, Silvia

PY - 2020/12/11

Y1 - 2020/12/11

N2 - Both, aberrant mast cell responses and complement activation contribute to allergic diseases. Since mast cells are highly responsive to C3a and C5a, while Interleukin-33 (IL-33) is a potent mast cell activator, we hypothesized that IL-33 critically regulates mast cell responses to complement anaphylatoxins. We sought to understand whether C3a and C5a differentially activate primary human mast cells, and probe whether IL-33 regulates C3a/C5a-induced mast cell activities. Primary human mast cells were generated from peripheral blood precursors or isolated from healthy human lung tissue, and mast cell complement receptor expression, degranulation, mediator release, phosphorylation patterns, and calcium flux were assessed. Human mast cells of distinct origin express constitutively higher levels of C3aR1 than C5aR1, and both receptors are downregulated by anaphylatoxins. While C3a is a potent mast cell degranulation inducer, C5a is a weaker secretagogue with more delayed effects. Importantly, IL-33 potently enhances the human mast cell reactivity to C3a and C5a (degranulation, cytokine and chemokine release), independent of changes in C3a or C5a receptor expression or the level of Ca2+ influx. Instead, this reflects differential dynamics of intracellular signaling such as ERK1/2 phosphorylation. Since primary human mast cells respond differentially to anaphylatoxin stimulation, and that IL-33 is a key regulator of mast cell responses to complement anaphylatoxins, this is likely to aggravate Th2 immune responses. This newly identified cross-regulation may be important for controlling exacerbated complement- and mast cell-dependent Th2 responses and thus provides an additional rationale for targeting anti-IL33 therapeutically in allergic diseases.

AB - Both, aberrant mast cell responses and complement activation contribute to allergic diseases. Since mast cells are highly responsive to C3a and C5a, while Interleukin-33 (IL-33) is a potent mast cell activator, we hypothesized that IL-33 critically regulates mast cell responses to complement anaphylatoxins. We sought to understand whether C3a and C5a differentially activate primary human mast cells, and probe whether IL-33 regulates C3a/C5a-induced mast cell activities. Primary human mast cells were generated from peripheral blood precursors or isolated from healthy human lung tissue, and mast cell complement receptor expression, degranulation, mediator release, phosphorylation patterns, and calcium flux were assessed. Human mast cells of distinct origin express constitutively higher levels of C3aR1 than C5aR1, and both receptors are downregulated by anaphylatoxins. While C3a is a potent mast cell degranulation inducer, C5a is a weaker secretagogue with more delayed effects. Importantly, IL-33 potently enhances the human mast cell reactivity to C3a and C5a (degranulation, cytokine and chemokine release), independent of changes in C3a or C5a receptor expression or the level of Ca2+ influx. Instead, this reflects differential dynamics of intracellular signaling such as ERK1/2 phosphorylation. Since primary human mast cells respond differentially to anaphylatoxin stimulation, and that IL-33 is a key regulator of mast cell responses to complement anaphylatoxins, this is likely to aggravate Th2 immune responses. This newly identified cross-regulation may be important for controlling exacerbated complement- and mast cell-dependent Th2 responses and thus provides an additional rationale for targeting anti-IL33 therapeutically in allergic diseases.

M3 - Article

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

ER -