β2 integrins rather than β1 integrins mediate Alternaria-induced group 2 innate lymphoid cell trafficking to the lung

J Allergy Clin Immunol. 2018 Jan;141(1):329-338.e12. doi: 10.1016/j.jaci.2017.03.010. Epub 2017 Mar 30.

Abstract

Background: Group 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 after Alternaria exposure is unknown.

Objective: We examined whether human (lung, lymph node, and blood) and mouse lung ILC2s express β1 and β2 integrin adhesion molecules and whether these integrins are required for trafficking of ILC2s into the lungs of mice.

Methods: Human and mouse ILC2s were assessed for surface expression of β1 and β2 integrin adhesion molecules by using flow cytometry. The role of β1 and β2 integrins in ILC2 trafficking to the lungs was assessed by in vivo blocking of these integrins before airway exposure to Alternaria in mice.

Results: Both human and mouse lung ILC2s express high levels of β1 and β2 integrin adhesion receptors. Intranasal administration of Alternaria challenge reduced ILC2 numbers in the bone marrow and concurrently increased blood and lung ILC2 numbers. In vivo blocking of β2 integrins (CD18) significantly reduced ILC2 numbers 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 numbers.

Conclusion: ILC2 numbers increase 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.

Keywords: Alternaria alternata; Group 2 innate lymphoid cell; adhesion; integrin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alternaria / immunology*
  • Animals
  • Apoptosis / immunology
  • Biomarkers
  • Bone Marrow / immunology
  • Bone Marrow / metabolism
  • CD18 Antigens / genetics
  • CD18 Antigens / metabolism*
  • Cytokines / metabolism
  • Flow Cytometry
  • Gene Expression
  • Humans
  • Immunity, Innate*
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism*
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • L-Selectin / genetics
  • L-Selectin / metabolism
  • Lung / immunology*
  • Lung / metabolism*
  • Lung / pathology
  • Lymphocyte Count
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / metabolism*
  • Mice
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • Biomarkers
  • CD18 Antigens
  • Cytokines
  • Integrin beta1
  • Intercellular Adhesion Molecule-1
  • L-Selectin