β2 Integrins Rather than β1 Integrins Mediate Alternaria-induced ILC2 Trafficking to the Lung

Publication date: Available online 30 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Maya R. Karta, Peter S. Rosenthal, Andrew Beppu, Christine Y. Vuong, Marina Miller, Sudipta Das, Richard C. Kurten, Taylor A. Doherty, David H. Broide
BackgroundGroup 2 innate lymphoid cells (ILC2s) expand in the lungs of mice during type 2 inflammation induced by the fungal allergen Alternaria alternata. The increase in ILC2 numbers in the lung has been largely attributed to local proliferation and whether ILC2s migrate from the circulation to the lung following Alternaria exposure is unknown.ObjectiveWe examined whether human (lung, lymph node, blood) and mouse lung ILC2s express β1 and β2 integrin adhesion molecules, and whether these integrins are required for trafficking of ILC2 into the lungs of miceMethodsHuman and mouse ILC2s were assessed for surface expression of β1 and β2 integrins adhesion molecules by flow cytometry. The role of β1 and β2 integrins in ILC2 trafficking to the lungs was assessed by in vivo blocking of these integrins prior to airway exposure to Alternaria in mice.ResultsBoth human and mouse lung ILC2s express high levels of β1 and β2 integrin adhesion receptors. Intranasal administration of Alternaria challenge reduced ILC2s in the bone marrow and concurrently increased blood and lung ILC2 levels. In vivo blocking of β2 integrins (CD18) significantly reduced ILC2 levels in the lungs, but did not alter ILC2 proliferation, apoptosis, and function. In contrast, in vivo blocking of β1 integrins or α4 integrins did not affect lung ILC2 levels.ConclusionILC2s increase in number in the mouse lung not only through local proliferation, but also through trafficking from the circulation into the lung using β2 rather than β1 or α4 integrins.

Teaser

ILC2s, which express high levels of Th2 cytokines, are not only resident in the lung, but also traffic from the bone marrow to the lung upon exposure to Alternaria, an allergen associated with severe asthma.


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