Knight, JohnLee, Seung-HyoRoberts, LuzSmith, C. WayneWeiss, ScottKheradmand, FarrahCorry, David B.2016-05-172014Knight, John M., Seung-Hyo Lee, Luz Roberts, C. Wayne Smith, Scott T. Weiss, Farrah Kheradmand, and David B. Corry. 2014. CD11a polymorphisms regulate TH2 cell homing and TH2-related disease. Journal of Allergy and Clinical Immunology 133, no. 1: 189–197.e8. doi:10.1016/j.jaci.2013.03.049.0091-6749http://nrs.harvard.edu/urn-3:HUL.InstRepos:27005841Background: 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.en-USasthmaallergic diseaseCD11acell homingpolymorphismallelecongenicbiomarkerJournal Article2016-05-1710.1016/j.jaci.2013.03.049