TY - JOUR

T1 - IL-33 delivery induces serous cavity macrophage proliferation independent of interleukin-4 receptor alpha

AU - Jackson-Jones, Lucy H

AU - Rückerl, Dominik

AU - Svedberg, Freya

AU - Duncan, Sheelagh

AU - Maizels, Rick M

AU - Sutherland, Tara E

AU - Jenkins, Stephen J

AU - McSorley, Henry J

AU - Bénézech, Cécile

AU - MacDonald, Andrew S

AU - Allen, Judith E

N1 - © 2016 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2016/10

Y1 - 2016/10

N2 - IL-33 plays an important role in the initiation of type-2 immune responses, as well as the enhancement of type 2 effector functions. Engagement of the IL-33 receptor on macrophages facilitates polarization to an alternative activation state by amplifying IL-4 and IL-13 signaling to IL-4Rα. IL-4 and IL-13 also induce macrophage proliferation but IL-33 involvement in this process has not been rigorously evaluated. As expected, in vivo delivery of IL-33 induced IL-4Rα-dependent alternative macrophage activation in the serous cavities. IL-33 delivery also induced macrophages to proliferate but, unexpectedly, this was independent of IL-4Rα signaling. In a filarial nematode infection model in which IL-4Rα-dependent alternative activation and proliferation in the pleural cavity is well described, IL-33R was essential for alternative activation but not macrophage proliferation. Similarly, during Alternaria alternata induced airway inflammation, which provokes strong IL-33 responses, we observed that both IL-4Rα and IL-33R were required for alternative activation, while macrophage proliferation in the pleural cavity was still evident in the absence of either receptor alone. Our data show that IL-33R and IL-4Rα promote macrophage proliferation independently of each other, but both are essential for induction of alternative activation.

AB - IL-33 plays an important role in the initiation of type-2 immune responses, as well as the enhancement of type 2 effector functions. Engagement of the IL-33 receptor on macrophages facilitates polarization to an alternative activation state by amplifying IL-4 and IL-13 signaling to IL-4Rα. IL-4 and IL-13 also induce macrophage proliferation but IL-33 involvement in this process has not been rigorously evaluated. As expected, in vivo delivery of IL-33 induced IL-4Rα-dependent alternative macrophage activation in the serous cavities. IL-33 delivery also induced macrophages to proliferate but, unexpectedly, this was independent of IL-4Rα signaling. In a filarial nematode infection model in which IL-4Rα-dependent alternative activation and proliferation in the pleural cavity is well described, IL-33R was essential for alternative activation but not macrophage proliferation. Similarly, during Alternaria alternata induced airway inflammation, which provokes strong IL-33 responses, we observed that both IL-4Rα and IL-33R were required for alternative activation, while macrophage proliferation in the pleural cavity was still evident in the absence of either receptor alone. Our data show that IL-33R and IL-4Rα promote macrophage proliferation independently of each other, but both are essential for induction of alternative activation.

KW - Alternaria

KW - Alternariosis

KW - Animals

KW - Cell Proliferation

KW - Cells, Cultured

KW - Filariasis

KW - Filarioidea

KW - Interleukin-1 Receptor-Like 1 Protein

KW - Interleukin-33

KW - Macrophage Activation

KW - Macrophages

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Knockout

KW - Pleural Cavity

KW - Receptors, Cell Surface

KW - Serous Membrane

KW - Signal Transduction

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/eji.201646442

DO - 10.1002/eji.201646442

M3 - Journal article

C2 - 27592711

VL - 46

SP - 2311

EP - 2321

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 10

ER -