Remission of peanut allergy is associated with rewiring of allergen‐driven T helper 2‐related gene networks. Issue 10 (25th May 2022)

• Record Type: Journal Article
• Authors: Ashley, Sarah E.; Jones, Anya C.; Anderson, Denise; Holt, Patrick G.; Bosco, Anthony; Tang, Mimi L. K.
• Is Part Of: Allergy. Volume 77:Issue 10(2022)
• Page Start: 3015
• Page End: 3027
• Publication Date: 2022-05-25
• Subjects: CD4+ T cells -- food oral immunotherapy -- network analysis -- remission of allergy -- sustained unresponsiveness; Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.15324
• Languages: English
• ISSNs: 0105-4538

Abstract

Abstract: Background: The immunological changes underpinning acquisition of remission (also called sustained unresponsiveness) following food immunotherapy remain poorly defined. Limited access to effective therapies and biosamples from treatment responders has prevented progress. Probiotic peanut oral immunotherapy is highly effective at inducing remission, providing an opportunity to investigate immune changes. Methods: Using a systems biology approach, we examined gene co‐expression network patterns in peanut‐specific CD4 + T cell responses before and after probiotic and peanut oral immunotherapy in subjects enrolled in the PPOIT‐001 randomized trial: Responders who attained remission ( n = 16), placebo‐treated who remained allergic ( n = 16). Results: Acquisition of remission was associated with rewiring of gene network patterns, which was characterized by integration of T helper 2 and interferon signalling modules, markedly reduced T helper 2 gene connectivity, and shutdown in co‐expression activity between T helper 2 effectors and cell cycle regulators. Conclusion: The immunological changes underlying remission following peanut oral immunotherapy are mediated by reprogramming of T helper 2‐associated gene networks in the CD4 + T cell compartment. Findings provide insight into immune mechanisms driving the acquisition of remission following oral immunotherapy, paving the way for the development of improved approaches to induce remission/sustained unresponsiveness in patients with food allergy. Abstract : We examined longitudinal changes in gene co‐expression networks in peanut‐specific CD4 + T cells from participants with remission following oral immunotherapy (OIT) ( n = 16) and placebo‐treated who remained allergic ( n = 16). Remission was associated with emergence of a regulatory module dominated by type 1 interferon signalling and collapse of the allergic T helper 2 module, with Th2 genes incorporated within the regulatory module. Findings provide insight into immune mechanisms driving the acquisition of remission following oral immunotherapy.Abbreviations: CCNB, cyclin B; CDK1, cyclin dependent kinase 1; CEP55, centrosomal protein 55; DC, dendritic cell; IFN, interferon; IL, interleukin; PBMC, peripheral blood mononuclear cell; PPOIT, probiotic + peanut oral immunotherapy; Th2, T helper 2