Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma

Abstract

BackgroundAllergic rhinitis (AR) affects up to 80% of children with asthma and increases asthma severity. Thymic stromal lymphopoietin (TSLP) is a key mediator of allergic inflammation. The role of the TSLP gene (TSLP) in the pathogenesis of AR has not been studied.ObjectiveTo test for associations between variants in TSLP, TSLP-related genes, and AR in children with asthma.MethodsWe genotyped 15 single nucleotide polymorphisms (SNPs) in TSLP, OX40L, IL7R, and RXRα in three independent cohorts: 592 asthmatic Costa Rican children and their parents, 422 nuclear families of North American children with asthma, and 239 Swedish children with asthma. We tested for associations between these SNPs and AR. As we previously reported sex-specific effects for TSLP, we performed overall and sex-stratified analyses. We additionally performed secondary analyses for gene-by-gene interactions.ResultsAcross the three cohorts, the T allele of TSLP SNP rs1837253 was undertransmitted in boys with AR and asthma as compared to boys with asthma alone. The SNP was associated with reduced odds for AR (odds ratios ranging from 0.56 to 0.63, with corresponding Fisher's combined P value of 1.2 × 10-4). Our findings were significant after accounting for multiple comparisons. SNPs in OX40L, IL7R, and RXRα were not consistently associated with AR in children with asthma. There were nominally significant interactions between gene pairs.ConclusionsTSLP SNP rs1837253 is associated with reduced odds for AR in boys with asthma. Our findings support a role for TSLP in the pathogenesis of AR in children with asthma.

Inhibition of IL-32 and TSLP production through the attenuation of caspase-1 activation in an animal model of allergic rhinitis by Naju Jjok (Polygonum tinctorium)

“…Thymic stromal lymphopoietin (TSLP) is a central factor in allergic inflammation and allergy-related diseases, including atopic dermatitis (AD), asthma and AR (15)(16)(17). TSLP is expressed and produced by caspase-1 and NF-κB in mast cells (18,19).…”

Distribución de tres polimorfismos del gen TSLP en población afrodescendiente de San Basilio de Palenque, Colombia

“…En Colombia estas enfermedades afectan a más del 20 % de la población y en reportes preliminares se sugiere un incremento de sus cifras en los últimos años (Caraballo LR, comunicación personal). Como ya se ha mencionado, el gen TSLP se ha vinculado como un gen de propensión al desarrollo de estas enfermedades y demás alteraciones relacionadas, en poblaciones hispanas, afroamericanas y europeas (13,14). Por tal motivo, todos los estudios genéticos que vinculen polimorfismos de este gen, permitirán entender más a fondo los mecanismos que regulan la expresión y los efectos de esta citocina en el desarrollo de la respuesta inmunitaria hacia un fenotipo Th2 como es el caso de los estudios de asociación y epigenéticos, así como también, inferir la posible influencia de estas variaciones genéticas en poblaciones de mezcla reciente como la de Cartagena de Indias.…”

“…De igual manera, Hunninghake, et al, observaron que en individuos hispanos, afroamericanos y europeos, el alelo T de rs1837253 se asoció con un menor riesgo de asma en hombres, mientras que el alelo T de rs2289276 se asoció con un menor riesgo en mujeres (13). En estas mismas poblaciones, Bunyavanich, et al, demostraron un riesgo reducido de rinitis alérgica en niños asmáticos (14). Por otra parte, Gao, et al, reportaron que el polimorfismo rs17551370 se asoció significativamente con los niveles séricos de IgE total en población afroamericana.…”

Socioeconomic impact of traditional Korean medicine, Pyeongwee-San (KMP6) as an anti-allergic inflammatory drug

“…Thymic stromal lymphopoietin (TSLP) is associated with AR and AD (Bunyavanich et al, 2011;Ziegler et al, 2010). It might initiate Th2 polarization through an OX40-dependent mechanism that affects dendritic cells (DC) activity (Ziegler et al, 2010).…”