Details

Autor(en) / Beteiligte

• Woytschak, Janine
• Keller, Nadia
• Krieg, Carsten
• Impellizzieri, Daniela
• Thompson, Robert W.
• Wynn, Thomas A.
• Zinkernagel, Annelies S.
• Boyman, Onur

Titel

Type 2 Interleukin-4 Receptor Signaling in Neutrophils Antagonizes Their Expansion and Migration during Infection and Inflammation

Ist Teil von

• Immunity (Cambridge, Mass.), 2016-07, Vol.45 (1), p.172-184

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Neutrophils are the first immune cells recruited to sites of inflammation and infection. However, patients with allergic disorders such as atopic dermatitis show a paucity of skin neutrophils and are prone to bacterial skin infections, suggesting that allergic inflammation curtails neutrophil responses. Here we have shown that the type 2 cell signature cytokine interleukin-4 (IL-4) hampers neutrophil expansion and migration by antagonizing granulocyte colony-stimulating factor (G-CSF) and chemokine receptor-mediated signals. Cutaneous bacterial infection in mice was exacerbated by IL-4 signaling and improved with IL-4 inhibition, each outcome inversely correlating with neutrophil migration to skin. Likewise, systemic bacterial infection was worsened by heightened IL-4 activity, with IL-4 restricting G-CSF-induced neutrophil expansion and migration to tissues by affecting CXCR2-CXCR4 chemokine signaling in neutrophils. These effects were dependent on IL-4 acting through type 2 IL-4 receptors on neutrophils. Thus, targeting IL-4 might be beneficial in neutropenic conditions with increased susceptibility to bacterial infections. [Display omitted] •Cutaneous and systemic bacterial infections are exacerbated by IL-4 signaling•IL-4 restricts neutrophil expansion in and migration from bone marrow to tissues•IL-4 opposes G-CSF effects by direct action on neutrophils via type 2 IL-4Rs•IL-4 interferes with CXCR2-CXCR4 and p38 MAPK-PI3K regulation in neutrophils Although neutrophils usually predominate acute inflammatory conditions, they are conspicuously absent in many allergic disorders. Boyman and colleagues demonstrate that the type 2 cell signature cytokine interleukin-4 (IL-4) curtails neutrophil recruitment and migration by signaling via type 2 IL-4 receptors that become upregulated on neutrophils upon inflammation and infection.