Association of Toll‐like receptor 2 rs111200466 polymorphism with low serum levels of IL‐33 in early childhood

Abstract

TLR2 is one of 10 human TLRs, which plays an important role in the recognition of pathogens and activation of the innate immunity via NF‐κB pathway. NF‐κB activation induces the expression of various pro‐inflammatory genes. This study examines the effect of TLR2 polymorphisms on the production of blood pro‐inflammatory cytokines in healthy Finnish children. One hundred forty‐six children who participated in a prospective observational birth cohort study in Turku, Finland, were included. DNA samples were analysed by PCR‐based sequencing for two common TLR2 polymorphisms (rs5743708 Arg753Gln; rs111200466–196 to –174del). Serum concentrations of IL‐33, IL‐31, IL‐17A and IL‐17F were measured by multiplex immunoassay and sST2 by ELISA in children at the age of 13 months. Children with variant type of TLR2 rs111200466 (ins/del or del/del) had significantly lower level of serum IL‐33 (median, 0.00 pg/mL; IQR 0.00–17.60) than those with ins/ins type of TLR2 (19.81 pg/mL; IQR 0.00–51.78) (p = 0.0001). Almost all study subjects had serum concentrations of IL‐17A, IL‐17F and IL‐31 below the detection limit and therefore not included in the final analyses. No differences in levels of above four cytokines and sST2 were found between TLR2 rs5743708 genotypes (GG and GA). Our results indicated that the TLR2 rs111200466 deletion was associated with a low level of serum IL‐33, suggesting that the polymorphism may impair the production of IL‐33.

ST2 and IL‐33 polymorphisms and the development of childhood asthma: a prospective birth cohort study in Finnish children

“…This finding suggests that children with the polymorphism of TLR2 may have impaired production of IL‐33, which could contribute to the protection against asthma development. However, we did not find similar correlation between TLR2 rs111200466 polymorphism and serum sST2 levels [17]. Here we wanted further to study the effects of these SNPs of ST2 and IL‐33 on serum sST2 and IL‐33 levels and in addition, to investigate whether these polymorphisms are associated with the susceptibility to recurrent wheezing or asthma.…”

“…We have previously shown with the same cohort that low concentration of serum sST2, but not IL‐33, at early age (13 months) is associated with a higher risk for development of asthma at 7 years of age in Finnish children [16]. In addition, we found that subjects who carry a 23 bp deletion in the promoter of TLR2 (rs111200466) produced lower level of serum IL‐33 compared to those who carry the insertion [17]. This finding suggests that children with the polymorphism of TLR2 may have impaired production of IL‐33, which could contribute to the protection against asthma development.…”

Salivary IL‐33 and sST2 levels in relation to TLR2 rs111200466 polymorphism and periodontitis

“…Indeed, TLR2 rs3804100, rs1898830 and rs5743708 single nucleotide polymorphisms, which lead to variations in the amino acid sequence of TLR2, have been related to periodontal tissue destruction (Shan et al, 2020;Takahashi et al, 2011). Recently, TLR2 rs111200466 deletion was revealed to be associated with altered serum IL-33 levels in children (Teräsjärvi et al, 2023). Based on this background information, we hypothesised that there is an association between periodontitis and elevated salivary IL-33 and sST2 levels, and this could be related to the presence of TLR2 rs111200466 polymorphism.…”