Research ArticleALLERGY

A Generally Applicable Translational Strategy Identifies S100A4 as a Candidate Gene in Allergy

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Science Translational Medicine  08 Jan 2014:
Vol. 6, Issue 218, pp. 218ra4
DOI: 10.1126/scitranslmed.3007410

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Modular Approach Nothing to Sneeze At

If genome-wide association studies have taught us anything, it’s that paring down genes potentially involved in specific diseases into viable therapeutic candidates can be an overwhelming task. Thousands of genes can be implicated, which then must be functionally validated. Now, Bruhn et al. take a modular approach to this problem in the context of allergy. They focus on genes co-regulated with the proallergic gene interleukin-13 (IL13).

The authors identified a T helper 2 (TH2) cell module using small interfering RNA–mediated knockdown of putative IL13-regulating transcription factors. They then further validated one of these genes, S100A4, which has previously been shown to be involved in inflammatory cell recruitment. Loss of S100A4 resulted in decreased allergy-associated immune responses both in vitro and in a mouse model. Moreover, blocking S100A4 with an antibody decreased allergic response both in their mouse model and in cells derived from allergic patients, which suggests that S100A4 may be a new therapeutic target for allergy.