ArticlePloS one2012
TBX21 and HLX1 polymorphisms influence cytokine secretion at birth.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- T-bet: biological functions, molecular mechanisms, and therapeutic applications: a systematic review.Frontiers in immunology · 2026Pooled it
- Frequency distribution of cytokine and associated transcription factor single nucleotide polymorphisms in Zimbabweans: Impact on schistosome infection and cytokine levels.PLoS neglected tropical diseases · 2022Article
- [Immune system and allergies-An unholy alliance].Der Internist · 2022Review
- Rs868058 in the Homeobox GeneBiology · 2022Article
- HLX affects cell cycle and proliferation in AML cells via the JAK/STAT signaling pathway.Oncology letters · 2020Article
- Review
- Article
- T-bet as a key regulator of mucosal immunity.Immunology · 2016Review
- Methylomic markers of persistent childhood asthma: a longitudinal study of asthma-discordant monozygotic twins.Clinical epigenetics · 2015Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTBX21 (T cell specific T-box transcription factor) and HLX1 (H.20-like homeobox 1) are crucial transcription factors of T(H)1-cells, inducing their differentiation and suppressing T(H)2 commitment, particularly important for early life immune development. This study investigated the influence of TBX21 and HLX1 single nucleotide polymorphisms (SNPs), which have previously been shown to be associated with asthma, on T(H)1/T(H)2 lineage cytokines at birth. METHODS AND
findingsCord blood mononuclear cells (CBMCs) of 200 neonates were genotyped for two TBX21 and three HLX1 SNPs. CBMCs were stimulated with innate (Lipid A, LpA; Peptidoglycan, Ppg), adaptive stimuli (house dust mite Dermatophagoides pteronyssinus 1, Derp1) or mitogen (phytohemagglutinin, PHA). Cytokines, T-cells and mRNA expression of T(H)1/T(H)2-related genes were assessed. Atopic diseases during the first 3 years of life were assessed by questionnaire answered by the parents. Carriers of TBX21 promoter SNP rs17250932 and HLX1 promoter SNP rs2738751 showed reduced or trendwise reduced (p≤0.07) IL-5, IL-13 and TNF-α secretion after LpA-stimulation. Carriers of HLX1 SNP rs2738751 had lower IL-13 levels following Ppg-stimulation (p = 0.08). Carriers of HLX1 exon 1 SNP rs12141189 showed increased IL-5 (LpA, p = 0.007; Ppg, p = 0.10), trendwise increased IL-13 (LpA), higher GM-CSF (LpA/Ppg, p≤0.05) and trendwise decreased IFN-γ secretion (Derp1+LpA-stimulation, p = 0.1). Homozygous carriers of HLX1 promoter SNP rs3806325 showed increased IL-13 and IL-6 (unstimulated, p≤0.03). In carriers of TBX21 intron 3 SNP rs11079788 no differences in cytokine secretion were observed. mRNA expression of T(H)1/T(H)2-related genes partly correlated with cytokines at protein level. TBX21 SNP rs11079788 carriers developed less symptoms of atopic dermatitis at 3 years of age (p = 0.03).
conclusionsPolymorphisms in TBX21 and HLX1 influenced primarily IL-5 and IL-13 secretion after LpA-stimulation in cord blood suggesting that genetic variations in the transcription factors essential for the T(H)1-pathway may contribute to modified T(H)2-immune responses already early in life. Further follow-up of the cohort is required to study the polymorphisms' relevance for immune-mediated diseases such as childhood asthma.
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