Exposure to Peanut Flour through Disturbed Skin Initiates Peanut Allergy via the T Follicular Helper T (Tfh) Cell-Dependent Pathway in Mice

RATIONALE: The mechanisms involved in development of peanut allergy are not fully understood. The goal of this project was to investigate the role of skin exposure to peanut products and immunological mechanisms involved in initiation of peanut allergy.

METHODS: Abdominal skin of naïve BALB/c mice was stripped with an adhesive tape. Mice were then exposed to peanut by painting the skin with peanut flour (PN-f) for 4 weeks. The plasma levels of peanut-specific IgE antibody were measured by ELISA. Mice were challenged with intraperitoneal (i.p.) injection of peanut extract, and clinical symptoms were monitored for 60 minutes. CD4⁺ T cells in draining lymph nodes (dLNs) were analyzed by FACS. A genetic model was used to dissect the roles for Tfh cells.

RESULTS: Mice that were exposed to PN-f through the disturbed skin produced PN-specific IgE antibody; no exogenous adjuvants were required. When sensitized mice were challenged by i.p. injection of PN extract, they showed clinical signs of acute systemic anaphylaxis, such as decreased core body temperature. Increased numbers of total Tfh cells (CD4⁺CXCR5⁺) and mature Tfh cells (CD4⁺CXCR5⁺PD-1⁺) were observed in dLN of PN-f-exposed mice. Furthermore, the mice deficient in Tfh cells (i.e. CXCR5fl/flCD4-Cre) produced significantly less peanut-specific IgE antibody, and they were protected from developing acute anaphylaxis.

CONCLUSIONS: Cutaneous exposure through the disturbed skin in mice initiates peanut allergy that is analogous to human peanut allergy. Tfh cells likely play a pivotal role in development of allergen-specific IgE antibodies and clinical outcomes in peanut allergy.