Targeting Pim1 kinase in the treatment of peanut allergy

Abstract

Introduction: Peanut sensitization is the most significant food allergen associated with life-threatening allergic reactions. Unlike many food sensitivities, peanut allergy often persists into adulthood. Presently, the only effective therapy is peanut avoidance. Effective preventative therapy requires an understanding of the pathways that lead to anaphylaxis. IgE and mast cell activation are essential contributors. The responsible pathways upstream are driven by pro-allergic T helper 2 differentiation and release of cytokines including interleukin-4 (IL-4) and IL-13.

Areas covered: The research utilized an experimental model of peanut-induced anaphylaxis in mice that mimics many of the responses seen in the human disease. Following peanut sensitization and challenge, clinical responses, intestinal inflammatory and immune cell interactions, and genetic and molecular events were monitored. For the first time, evidence for Pim1 kinase involvement was demonstrated in association with the downregulation of Runx3, a known silencer of the IL-4 gene locus. Evidence for Pim1 kinase involvement was shown through the use of a small molecule inhibitor of Pim1 kinase.

Expert opinion: Activation of Pim1 kinase and downregulation of Runx3 were essential to the development of peanut-induced intestinal anaphylaxis. Targeting of this Pim1 kinase-Runx3 axis may provide new therapeutic options in the prevention of life-threatening reactions to peanut.

Keywords::

• anaphylaxis
• peanut
• Pim1 kinase
• Runx3

Declaration of interest

EW Gelfand received funding from NIH grants HL-36577 and AI-77609. No payment was received in support of this article and the authors have no competing interests to declare.

Notes

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