IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation.

Abstract

Alternatively activated macrophages (AAM) play a crucial role in type 2 immunity. Mice deficient in ST2, a receptor for the latest member of the IL-1 family, IL-33, have impaired type 2 immune responses. We therefore reasoned that IL-33/ST2 signaling may be involved in the differentiation and activation of AAM during airway inflammation. We report here that IL-33 changed the quiescent phenotype of alveolar macrophages toward an AAM phenotype that expressed mannose receptor, IL-4Ralpha, and produced high levels of CCL24 and CCL17 in an IL-13-dependent manner during IL-33-induced airway inflammation. Neutralization of AAM-derived CCL24 led to an amelioration of IL-33-induced eosinophilia in the lungs. Moreover, depletion of alveolar macrophages reduced IL-33-induced airway inflammation. Additionally, the attenuated OVA-induced airway inflammation in ST2(-/-) mice was associated with a decrease in AAM differentiation. In vitro, IL-33 amplified IL-13-induced polarization of alveolar- and bone marrow-derived macrophage toward an AAM phenotype by increasing the expression of arginase I, Ym1, as well as the production of CCL24 and CCL17. IL-13/IL-4Ralpha signaling was crucial for IL-33-driven AAM amplification by inducing the expression of ST2L. Finally, we showed that IL-33 was more abundantly expressed in the lung epithelial cells of asthma patients than those from healthy controls, suggesting that IL-33 may be involved in lung macrophage activation in clinical asthma. Taken together, we demonstrate here that IL-33/ST2 plays a significant role in the amplification of AAM polarization and chemokine production which contribute to innate and Ag-induced airway inflammation.

• Authors: Mariola Kurowska-Stolarska, Bartosz Stolarski, Peter Kewin, Grace Murphy, Christopher J Corrigan, Sun Ying, Nick Pitman, Ananda Mirchandani, Batika Rana, Nico van Rooijen, Malcolm Shepherd, Charlie McSharry, Iain B McInnes, Damo Xu, Foo Y Liew
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 183 Issue 10 Pg. 6469-77 (Nov 15 2009) ISSN: 1550-6606 [Electronic] United States
• PMID: 19841166 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CCL17
• Chemokine CCL24
• IL33 protein, human
• Il1rl1 protein, mouse
• Interleukin-1 Receptor-Like 1 Protein
• Interleukin-13
• Interleukin-33
• Interleukins
• Receptors, Interleukin
• Receptors, Interleukin-1
• Receptors, Interleukin-4
• Recombinant Proteins
• ST2L protein, mouse
• Interleukin-4
• Ovalbumin

Topics

• Adult
• Animals
• Asthma (immunology, metabolism)
• Cell Polarity (immunology)
• Chemokine CCL17 (immunology, metabolism)
• Chemokine CCL24 (immunology, metabolism)
• Eosinophilia (immunology)
• Epithelial Cells (immunology, metabolism)
• Female
• Humans
• Inflammation (immunology, metabolism)
• Interleukin-1 Receptor-Like 1 Protein
• Interleukin-13 (immunology, metabolism)
• Interleukin-33
• Interleukin-4 (genetics, immunology, metabolism)
• Interleukins (immunology, metabolism)
• Lung (immunology, pathology)
• Macrophage Activation (immunology)
• Macrophages, Alveolar (immunology, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Middle Aged
• Ovalbumin (immunology)
• Receptors, Interleukin (genetics, immunology, metabolism)
• Receptors, Interleukin-1 (immunology, metabolism)
• Receptors, Interleukin-4 (genetics, immunology, metabolism)
• Recombinant Proteins (immunology, metabolism)
• Signal Transduction (immunology)