Toll-like receptor heterodimer variants protect from childhood asthma.pdf

Asthma and lower airway disease
Original articles
Toll-like receptor heterodimer variants protect from
childhood asthma
Michael S. D. Kormann, PhD,a Martin Depner, MSc,a Dominik Hartl, MD,a Norman Klopp, PhD,a,b Thomas Illig, PhD,a,b
Jerzy Adamski, PhD,c Christian Vogelberg, MD,d Stephan K. Weiland, MD,e  Erika von Mutius, MD,a
and Michael Kabesch, MDa Munich, Neuherberg, Dresden, and Ulm, Germany
Background: Early exposure to microbes reduces the risk for Conclusion: These results suggest that functional relevant TLR1
asthma. Toll-like receptors (TLRs) represent a major group of and TLR6 variants are directly involved in asthma development.
receptors for the specific recognition of pathogen-associated (J Allergy Clin Immunol 2008;122:86-92.)
molecular patterns of microbes capable of activating innate and
adaptive immunity. Key words: Asthma, atopic asthma, Toll-like receptor, heterodimer,
Objective: Because TLRs can influence key events in the induction polymorphism
and perpetuation of asthma and atopy, we sought to determine
whether ic alterations in TLR genes affect asthma risk. Chronic inflammatory diseases occurring at the interface of the
Methods: We systematically evaluated putatively anism with the environment, such as atopic asthma, inflam-
ic variants in all 10 human TLR genes for their association matory bowel disease, and eczema, increased steeply in many
with different asthma phenotypes in a case-control study (n 5 countries over the last According to new insights, skin
1872) by using matrix-assisted laser desorption/ionization time- and mucosa do not represent mere passive barriers but are cen-
of-flight genotyping. For polymorphisms showing association trally involved in plex and highly sophisticated system for
with atopic asthma, effects on gene and protein expression were the recognition of (and interaction with) the environment. How-
studied by means of RT-PCR and flow cytometry ex vivo. T-cell ever, if the interaction with