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CD11a polymorphisms regulate TH2 cell homing and TH2-related disease.

John M Knight1, Seung-Hyo Lee2, Luz Roberts3

  • 1Department of Pathology and Immunology, Baylor College of Medicine, Houston, Tex.

The Journal of Allergy and Clinical Immunology
|June 4, 2013
PubMed
Summary

Genetic variations in the CD11a gene influence T-helper 2 cell responses and allergic disease severity in mice and humans. Specific CD11a alleles impact immune cell adhesion and homing, affecting allergic phenotypes.

Keywords:
AHRAirway hyperreactivityAsthmaCAMPCD11aChildhood Asthma Management ProgramLDLFA-1Leukocyte function–associated antigen 1Linkage disequilibriumMIBDMetal ion binding domainOVAOvalbuminPEPhycoerythrinRagRecombination-activating geneSNPSingle nucleotide polymorphismT(H)2 cellWTWild-typealleleallergic diseasebiomarkercongenichomingpolymorphism

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Area of Science:

  • Immunology
  • Genetics
  • Allergy Research

Background:

  • T-helper 2 (TH2) cell-dependent diseases exhibit variable severity linked to unknown gene polymorphisms.
  • Integrin CD11a is a key factor in allergic responses, with its allelic variants potentially affecting allergic phenotypes.

Purpose of the Study:

  • Identify major CD11a allelic variants in mice and humans.
  • Determine the role of CD11a polymorphisms in allergic disease expression.

Main Methods:

  • Sequenced mouse CD11a alleles (C57BL/6 and BALB/c) to find polymorphisms.
  • Analyzed human CD11a single nucleotide polymorphisms against allergic disease data (HapMap project).
  • Created congenic mice to assess CD11a polymorphism effects in vivo and in vitro.

Main Results:

  • The BALB/c CD11a allele had a nonsynonymous change in the metal ion binding domain compared to C57BL/6.
  • BALB/c CD11a enhanced TH2-dependent diseases (Leishmania major, Aspergillus niger-induced lung allergy), while C57BL/6 CD11a suppressed them.
  • BALB/c CD11a increased T-cell adhesion to CD54 and TH2 cell lung homing; a human CD11a polymorphism associated with atopic disease.

Conclusions:

  • CD11a polymorphisms significantly impact TH2 cell homing.
  • These variations critically influence diverse TH2-dependent immunopathologic states.
  • CD11a allelic variants may affect the manifestation of human allergic diseases.