Project description:The objective of the study was to investigate how oral immunotherapy (OIT) for food allergy modulates inflammation and immune cell responses. The blood cell transcriptome of 50 children receiving egg OIT was profiled using peripheral blood mononuclear cell (PBMC) samples obtained at baseline and after 3 and 8 months of OIT.
Project description:BACKGROUND. Cow’s milk allergy (CMA) is the most common food allergy in young children. Treatment with oral immunotherapy (OIT) has shown efficacy but also high rates of adverse reactions. We sought to determine if baked milk (BM) OIT could reduce adverse reactions while still inducing desensitization, and to identify immunological correlates of successful BMOIT. METHODS. This phase II, randomized trial evaluated the safety and efficacy of BMOIT in children age 3-18 years. After the initial placebo-controlled first year of treatment, placebo-treated participants crossed over to active BMOIT for year two. Double-blind, placebo-controlled food challenges (DBPCFC) were conducted to BM after year one and to both BM and unheated milk (UM) after year two. IgG/IgE antibodies were measured along with cow’s milk (CM)-specific CD4 memory T cell populations, profiled using flow cytometry and scRNA-Seq. RESULTS. Twenty-one of 30 (70%) reached the primary endpoint of tolerating 4044mg of BM protein at month-24, and 11/30 tolerated ≥2000mg of UM. Dosing symptoms were common, but >98% were mild with no severe reactions. Immunological changes associated with desensitization included increased CM IgG4, CM+ FOXP3+ cells, and Tregs and corresponding decreases in CM IgE, CM+ Th2A cells, and CD154+ cells. T cell and antibody measurements were combined to build a model that predicted UM oral food challenge (OFC) outcomes. CONCLUSION. BMOIT was well tolerated and induced a substantial level of desensitization to baked and unheated milk. This desensitization corresponded to significant redistribution within antigen specific antibody and T cell compartments that provide novel insight into the mechanistic changes that occur with OIT treatment.
Project description:Cutaneous exposure to food antigen through impaired skin barrier has been shown to induce epicutaneous sensitization, and thereby cause IgE-mediated food allergy. We examined whether skin barrier impairment deteriorated food allergy symptoms in epicutaneously sensitized mice. To clarify the association between skin inflammation and food allergy symptoms, we analyzed gene expression at skin lesions using a GeneChip.
Project description:Food allergy affects an estimated 8% of children in the US, with increasing severity and global prevalence. Using single-cell RNA sequencing and paired TCR sequencing, we assessed the transcriptomes of CD154+ and CD137+ peanut-reactive T helper cells from 12 peanut-allergic patients longitudinally throughout peanut oral immunotherapy. These results demonstrate a differential response to OIT among subsets of peanut-reactive T helper cells, and indicate that non-Th2 activation signatures may be associated with clinical outcomes.
Project description:Peanut allergy is increasingly prevalent among children in the United States and other industrialized countries and is now estimated to affect approximately 2% of children. While there are currently no approved treatment options, peanut allergy usually persists into adulthood, can be life-threatening, and accounts for most deaths related to food allergy. Here, we track peanut-reactive CD4+ T effector (pTeff) cells using the CD154 up-regulation assay. We found that CRTH2+ pTeff cells and CCR6+ pTeff cells represent two mutually exclusive, non-overlapping cellular and molecular entities involved in food allergic diseases.
Project description:Oral immunotherapy (OIT) has been considered a promising approach for food allergies (FAs). However, the current OIT strategy is limited in terms of the long-term efficacy and safety. We have previously demonstrated that kakkonto, a traditional Japanese herbal medicine, suppresses the occurrence of allergic symptoms in a murine model of ovalbumin (OVA)-induced FA, which is attributed to the induction of the Foxp3+ CD4+ regulatory T cells. In this study, we established an OIT model using the FA mice with already established allergic symptoms and determined whether kakkonto could improve the efficacy of OIT. The OIT method consisted of initially administrating a very small amount of OVA and slowly increasing the amount. Allergic symptoms decreased in the OIT-treated FA mice. OIT significantly downregulated Th2 immune response-related gene expression in the FA mouse colon, and decreased a level of mouse mast cell protease-1, a marker of mast cell degranulation in the FA mouse plasma. Furthermore, the concomitant use of kakkonto significantly enhanced the effectiveness of OIT on the allergic symptoms, the Th2 immune responses and the mast cell degranulation in the OIT-treated FA mice. In addition, OIT significantly increased the population of Foxp3+ CD4+ regulatory T cells in the FA mouse colon, and this population was further increased by OIT in combination with kakkonto. Furthermore, the combined therapy with kakkonto reduced the expression of RA-degrading enzyme CYP26B1 mRNA in the FA mouse colon. These findings indicated that the combination of OIT with kakkonto represents a promising approach for FA treatment.
Project description:This study profiled the epigenomes and transcriptomes of total B cell populations from adolescents with peanut-only (single food allergy- SA) and multi-food allergy (MA).
Project description:This study profiled the epigenomes and transcriptomes of total nCD4T cell populations from adolescents with peanut-only (single food allergy- SA) and multi-food allergy (MA) at quiescence and following activation with anti-CD3/antiCD28
Project description:This study profiled the epigenomes and transcriptomes of total B cell populations from adolescents with peanut-only (single food allergy- SA) and multi-food allergy (MA). We found distinct epigenetic and transcriptomic differences between food allergic patients and controls, in addition to SA- and MA- group specific signatures, with