Follicular helper T cells are responsible for IgE responses to Der p 1 following house dust mite sensitization in mice

TY - JOUR

T1 - Follicular helper T cells are responsible for IgE responses to Der p 1 following house dust mite sensitization in mice

AU - Noble, Alistair

AU - Zhao, Jingyue

PY - 2016/6/6

Y1 - 2016/6/6

N2 - Background: Th2 cells have long been considered responsible for the switching of B cells to production of IgE during cognate interaction, primarily due to their expression of CD40L and secretion of IL-4. This concept has been challenged by the more recent definition of follicular helper T cells (Tfh) as the key T cell subset in B cell isotype switching, due to their physical location at the boundary of T cell:B cell areas in lymphoid follicles and ability to express IL-4 and CD40L. Objective: To determine whether Tfh cells are responsible for IgE responses to Der p 1 allergen after house dust mite (HDM)-induced allergic sensitization. Methods: Mice deficient in Tfh cells were sensitized to HDM and Der p 1- specific IgE measured by ELISA. Results: Mice with a mutation in T cell-expressed IL-6R were unable to expand Tfh populations after HDM sensitisation and their anti-Der p 1 IgE, IgG1 and total IgE responses were reduced by 80-90% compared to wild-type mice. These animals displayed unaltered lung Th2 and eosinophilic responses after intranasal HDM challenge and normal IL-4 production, but B cell infiltration of the airways was abrogated. Conclusions & Clinical Relevance: Our data indicate that Tfh cells are largely responsible for switching B cells to IgE synthesis, most likely via an IgG1+ intermediate. However Th2 cells are the major source of IL-4 during HDM sensitization and this might contribute to IgE synthesis at a stage distal ! $! to Tfh-mediated isotype switching. The IL-6/follicular helper T cell pathway is a potential therapeutic target in allergic disease.

AB - Background: Th2 cells have long been considered responsible for the switching of B cells to production of IgE during cognate interaction, primarily due to their expression of CD40L and secretion of IL-4. This concept has been challenged by the more recent definition of follicular helper T cells (Tfh) as the key T cell subset in B cell isotype switching, due to their physical location at the boundary of T cell:B cell areas in lymphoid follicles and ability to express IL-4 and CD40L. Objective: To determine whether Tfh cells are responsible for IgE responses to Der p 1 allergen after house dust mite (HDM)-induced allergic sensitization. Methods: Mice deficient in Tfh cells were sensitized to HDM and Der p 1- specific IgE measured by ELISA. Results: Mice with a mutation in T cell-expressed IL-6R were unable to expand Tfh populations after HDM sensitisation and their anti-Der p 1 IgE, IgG1 and total IgE responses were reduced by 80-90% compared to wild-type mice. These animals displayed unaltered lung Th2 and eosinophilic responses after intranasal HDM challenge and normal IL-4 production, but B cell infiltration of the airways was abrogated. Conclusions & Clinical Relevance: Our data indicate that Tfh cells are largely responsible for switching B cells to IgE synthesis, most likely via an IgG1+ intermediate. However Th2 cells are the major source of IL-4 during HDM sensitization and this might contribute to IgE synthesis at a stage distal ! $! to Tfh-mediated isotype switching. The IL-6/follicular helper T cell pathway is a potential therapeutic target in allergic disease.

U2 - 10.1111/cea.12750

DO - 10.1111/cea.12750

M3 - Article

SN - 0954-7894

VL - 46

SP - 1075

EP - 1082

JO - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

IS - 8

ER -