title: β2integrins rather than β1integrins mediate Alternaria-induced group 2 innate lymphoid cell trafficking to the lung.
abstract: 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.
  
  
  
  We examined whether human (lung, lymph node, and blood) and mouse lung ILC2s express β1and β2integrin adhesion molecules and whether these integrins are required for trafficking of ILC2s into the lungs of mice.
  
  
  
  Human and mouse ILC2s were assessed for surface expression of β1and β2integrin adhesion molecules by using flow cytometry. The role of β1and β2integrins in ILC2 trafficking to the lungs was assessed by in vivo blocking of these integrins before airway exposure to Alternaria in mice.
  
  
  
  Both human and mouse lung ILC2s express high levels of β1and β2integrin 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 β2integrins (CD18) significantly reduced ILC2 numbers in the lungs but did not alter ILC2 proliferation, apoptosis, and function. In contrast, in vivo blocking of β1integrins or α4integrins did not affect lung ILC2 numbers.
  
  
  
  ILC2 numbers increase in the mouse lung not only through local proliferation but also through trafficking from the circulation into the lung using β2rather than β1or α4integrins.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, Calif.
authors.forename: Maya R
authors.initials: MR
authors.lastname: Karta
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, Calif.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Rosenthal
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, Calif.
authors.forename: Andrew
authors.initials: A
authors.lastname: Beppu
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, Calif.
authors.forename: Christine Y
authors.initials: CY
authors.lastname: Vuong
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, Calif.
authors.forename: Marina
authors.initials: M
authors.lastname: Miller
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, Calif.
authors.forename: Sudipta
authors.initials: S
authors.lastname: Das
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, Ark.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Kurten
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, Calif.
authors.forename: Taylor A
authors.initials: TA
authors.lastname: Doherty
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, Calif. Electronic address: dbroide@ucsd.edu.
authors.forename: David H
authors.initials: DH
authors.lastname: Broide
mesh_terms: D000528:Alternaria / Q000276:immunology*; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015415:Biomarkers; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D019041:L-Selectin / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018821:CD18 Antigens; D016207:Cytokines; D019012:Integrin beta1; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin
keywords: Alternaria alternata; Group 2 innate lymphoid cell; adhesion; integrin