Aspergillus nidulans exposure induces sarcoid-like features in HLA-DR3 Tg mice: A mouse model of sarcoidosis.
Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B520
Abstract ID: 5157
Presenting Author:
Shaikh M Atif , Assistant Professor at Univ. of Colorado Anschutz Med. Campus
Abstract:
Sarcoidosis is a granulomatous inflammatory disorder that affects multiple organs but predominantly the lungs. Recently, we identified a T cell epitope belonging to NAD-dependent protein deacetylase (NDPD) of Aspergillus nidulans and found epitope-specific reactivity in the BAL samples of both US and Löfgren’s syndrome (LS) HLA-DR3+ sarcoidosis patients. Based on these findings we have developed a transgenic mouse model of sarcoidosis that expresses human HLA-DR3 gene. Our data demonstrate that HLA-DR3 Tg mice exposed to A. nidulans replicate major pulmonary features of human sarcoidosis, including accumulation of activated CD4+ T cells and development of non-necrotizing granulomatous inflammation containing multinucleated giant cells. Flow cytometry analysis showed increased activation of CD11c+HLA-DR+ dendritic cells characterized by the increased expression of co-stimulatory molecules (CD40, CD86). Additionally, we have observed an alteration in resident (CD11c+SigF+) and recruited macrophages (CD11cloCD11b+) in the lungs. ELISpot assays with purified CD4+ T cells from the exposed lung also demonstrate cellular heterogeneity among the CD4+ T cells consisting of Th1 and Th17 cells when stimulated ex-vivo with NDPD protein or A. nidulans lysate. Overall, our data establishes the potential of A. nidulans exposed HLA-DR3 Tg mice to be used as a model of sarcoidosis, which could serve as a valuable tool for advancing our understanding of the disease.
Aspergillus nidulans exposure induces sarcoid-like features in HLA-DR3 Tg mice: A mouse model of sarcoidosis.
Category
Poster and Podium (Block Symposium)