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Exploring causal correlations between circulating cytokines and atopic dermatitis: a bidirectional two-sample

Zhenquan Xuan1,2,3, Xuanyi Chen1,2,3, Weinan Zhou1,2,3

  • 1Dermatology Center, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Frontiers in Immunology
|July 26, 2024
PubMed
Summary

This study used Mendelian randomization to investigate causal links between 91 cytokines and atopic dermatitis (AD). Several cytokines, including IL-13, are identified as potential causes of AD, while others may be consequences.

Keywords:
Mendelian randomizationatopic dermatitiscytokinesimmunotherapyinflammation

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Area of Science:

  • Immunology
  • Genetics
  • Dermatology

Background:

  • Observational studies suggest associations between cytokines and atopic dermatitis (AD), but causal relationships are unclear.
  • Understanding these links is crucial for developing targeted therapies for AD.

Purpose of the Study:

  • To explore causal correlations and the direction of effects between 91 circulating cytokines and atopic dermatitis (AD).

Main Methods:

  • Two-sample Mendelian randomization (MR) analyses were performed using genome-wide association study (GWAS) summary statistics.
  • Reverse MR analyses investigated potential reverse causation.
  • Pleiotropy, heterogeneity tests, and validation using transcriptome and peripheral blood mononuclear cells (PBMCs) data assessed robustness.

Main Results:

  • Several cytokines, including Interleukin (IL)-13, IL-18 Receptor 1, Tumor necrosis factor ligand superfamily member 14 (TNFSF14), and TNF-related activation-induced cytokine (TRANCE), were suggestively associated with AD risk.
  • Some cytokines, like Axin-1 and CXCL5, were suggested as consequences of AD.
  • IL-13, IL-18R1, TNFSF14, and TRANCE showed upregulation in both lesional skin and PBMCs of AD patients.

Conclusions:

  • Specific cytokines (IL-13, IL-18R1, TNFSF14, TRANCE, CXCL11, IL-33, TNF-beta, CD5) appear to be upstream factors in AD development.
  • A subset of circulating cytokines may be downstream consequences of AD.