CD11a polymorphisms regulate TH2 cell homing and T H2-related disease

John M. Knight, Seung Hyo Lee, Luz Roberts, C. Wayne Smith, Scott T. Weiss, Farrah Kheradmand, David Corry

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background: TH2-dependent diseases vary in severity according to genotype, but relevant gene polymorphisms remain largely unknown. The integrin CD11a is a critical determinant of allergic responses, and allelic variants of this gene might influence allergic phenotypes. Objective: We sought to determine major CD11a allelic variants in mice and human subjects and their importance to allergic disease expression. Methods: We sequenced mouse CD11a alleles from C57BL/6 and BALB/c strains to identify major polymorphisms; human CD11a single nucleotide polymorphisms were compared with allergic disease phenotypes as part of the international HapMap project. Mice on a BALB/c or C57BL/6 background and congenic for the other strain's CD11a allele were created to determine the importance of mouse CD11a polymorphisms in vivo and in vitro. Results: Compared with the C57BL/6 allele, the BALB/c CD11a allele contained a nonsynonymous change from asparagine to aspartic acid within the metal ion binding domain. In general, the BALB/c CD11a allele enhanced and the C57BL/6 CD11a allele suppressed TH2 cell-dependent disease caused by the parasite Leishmania major and allergic lung disease caused by the fungus Aspergillus niger. Relative to the C57BL/6 CD11a allele, the BALB/c CD11a allele conferred both greater T-cell adhesion to CD54 in vitro and enhanced TH2 cell homing to lungs in vivo. We further identified a human CD11a polymorphism that significantly associated with atopic disease and relevant allergic indices. Conclusions: Polymorphisms in CD11a critically influence TH2 cell homing and diverse TH2-dependent immunopathologic states in mice and potentially influence the expression of human allergic disease.

Original languageEnglish (US)
Pages (from-to)189-197.e8
JournalJournal of Allergy and Clinical Immunology
Volume133
Issue number1
DOIs
StatePublished - Jan 2014

Keywords

  • allele
  • allergic disease
  • Asthma
  • biomarker
  • CD11a
  • congenic
  • homing
  • polymorphism
  • T2 cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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