Federal Project Grant Award Summary

The National Institute of Allergy and Infectious Diseases (NIAID) awarded The Washington University a Project Grant totaling $233,250.00 under the Allergy and Infectious Diseases Research program (CFDA 93.855) for the period June 1, 2026 through May 31, 2028. This project focuses on elucidating the mechanisms and identifying therapeutic targets for a novel inborn error of immunity caused by gain-of-function variants in Toll-Like Receptor 8 (TLR8). The research deliverables include mechanistic studies of TLR8 gain-of-function disease utilizing newly developed transgenic mouse models that conditionally express wild-type and gain-of-function human TLR8, addressing critical gaps in understanding how TLR8 mutations lead to clinical manifestations including profound neutropenia, recurrent infections, lymphoproliferation, and bone marrow failure.

The research outputs will contribute to understanding myeloid cell dysfunction and inflammatory cytokine production in disease pathogenesis, with the ultimate goal of identifying potential therapeutic interventions for patients with TLR8 gain-of-function disease. Given the limited availability of targeted therapies and the demonstrated efficacy of hematopoietic stem cell therapy in affected patients, this project addresses a significant clinical need by providing mechanistic insights into disease etiology and potential treatment strategies for this recently recognized immunologic disorder.