Innate Immune Response Patterns to Autoantigen-Associated RNA

Project: Research project

Description

DESCRIPTION (provided by applicant): This proposal focuses on lung disease in anti-RNP autoimmunity, the leading cause of death in Mixed Connective Tissue Disease, and a significant clinical issue in RNP+ lupus. Based on preliminary data in a murine model of anti-RNP autoimmunity and human studies, we hypothesize that a subset of CD11c+ CD11bhigh CD103- myeloid dendritic cells acting through TLR-inducible TRIF-mediated pathways play a central role in the pathogenesis of anti-RNP autoimmune lung disease. In this proposal, we will test this hypothesis with studies in animal models. In Aim 1, we will assess the relevance of TRIF to anti-RNP lung disease by direct immunization and adoptive transfer studies with TRIF-/- mice. In Aim 2, we will assess the relevance of CD11b+ mDC's to anti-RNP lung disease using depletion studies with clodronate or antibodies to DC surface markers, and we will test the therapeutic efficacy of a novel immunosuppressive therapeutic agent that targets CD11b-expressing cells in anti-RNP lung disease. These studies will lead to improved understanding and potentially to novel treatment approaches for a spectrum of autoimmune disease for which current treatments have not been efficacious.
StatusFinished
Effective start/end date10/1/139/30/17

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Innate Immunity
Lung Diseases
RNA
Autoimmunity
Autoimmune Diseases
Clodronic Acid
Mixed Connective Tissue Disease
Adoptive Transfer
Myeloid Cells
Therapeutics
Immunosuppressive Agents
Dendritic Cells
Cause of Death
Immunization
Animal Models
To autoantigen
Antibodies

ASJC

  • Medicine(all)