The Role and Mechanism of Aberrant Dendritic Cell Function in Autoimmunity

Identifying a novel molecular regulator of tolerogenic dendritic cell function, this project uncovers how its loss triggers spontaneous multiorgan autoimmunity and exacerbates lupus — revealing a clinically relevant pathway in immune tolerance.
Complete Other Systemic Diseases Systemic Lupus Erythematosus (SLE) Adaptive Immunity Animal Models Bioinformatics Biological & Mechanistic Cytokine Signaling Data-Driven & Quantitative Disease Subtyping Experimental Platforms & Models Human Cohorts Human Genetics Immune Tolerance Innate Immunity Precision Medicine T Cell Biology Therapeutic Development Translational & Clinical

Funding Year: 2023

Project Overview

Dendritic cells (DCs) play a dual role in the immune system: initiating protective responses against pathogens and tumors while also promoting immune tolerance to prevent autoimmunity. Aberrant DC activity has been implicated in diseases such as systemic lupus erythematosus (SLE), but the molecular mechanisms governing tolerogenic DC function have remained poorly understood. This project identified a key molecular regulator that is preferentially expressed in DCs and whose deletion impairs their function, leading to aberrant maturation, loss of immune tolerance, and spontaneous multiorgan autoimmune inflammation in mouse models. Critically, deletion of this regulator also exacerbated SLE-like disease, and the gene has recently been associated with human SLE — collectively pointing to a novel and clinically relevant pathway in the molecular control of immune tolerance.

Impact & Innovation

Finding the molecular switch behind immune tolerance

 

This project identified a master regulator of dendritic cell homeostatic maturation — one whose loss triggers spontaneous multiorgan autoimmunity and exacerbates lupus-like disease, with confirmed genetic links to human SLE.

  • Provided direct causal evidence for a novel molecular pathway governing peripheral immune tolerance — a longstanding open question in autoimmunity
  • Demonstrated that loss of this DC-specific gene drives aberrant maturation, multiorgan inflammation, and exacerbated SLE — catalyzing NIH R21 funding
  • Advances the Consortium’s Shared Mechanisms Across Autoimmune Diseases pillar by linking a novel immune tolerance regulator directly to human lupus
Research Approach

A framework designed for discovery

This project combined genetic mouse models with molecular and cellular immunology to identify and characterize a key regulator of tolerogenic dendritic cell function. The work moved from gene identification and functional characterization through disease modeling and translational linkage to human SLE.

Genetic deletion of a candidate DC regulator in mouse models, analysis of DC maturation and immunostimulatory molecule expression in the steady state, and induction of SLE-like disease to assess the impact of regulator loss on autoimmune severity and progression.

Genetically modified mouse models with DC-specific deletion of the candidate regulator, steady-state and autoimmune disease phenotyping datasets, and human SLE genetic association data linking the regulator to clinical disease.

Elucidation of the molecular pathway by which this regulator controls homeostatic DC maturation and peripheral immune tolerance, with direct translational relevance to human SLE and other systemic autoimmune diseases. Findings support the gene as a potential therapeutic target and provide the mechanistic foundation for ongoing NIH-funded investigation.

Investigators & Institutions

Powering the science

Colton Centers & Institutions

Judith & Stewart Colton Center for Autoimmunity at NYU Langone Health

NYU Grossman School of Medicine

Research Outputs

From insight to impact

Publications

Transcription factor Etv3 controls the tolerogenic function of dendritic cells

Science
Adams, NM; Martinez-Krams, D; Esteva, E; Ra, AC; Alexiou, AI; Jin, H; Yun, TJ; Tellaoui, RS; Mudianto, T; Vollmer, E; Novikova, E; Tan, Y; Huntley, W; Krichevsky, O; Dolgalev, I; Izmirly, P; Buyon, JP; Moreira, AL; Lund, AW; Reizis, B February 2026
Adaptive ImmunityAnimal ModelsBioinformaticsBiological & MechanisticCytokine SignalingData-Driven & QuantitativeDisease SubtypingExperimental Platforms & ModelsHuman CohortsImmune ToleranceInnate ImmunityPrecision MedicineTranslational & ClinicalOtherSystemic DiseasesSystemic Lupus Erythematosus (SLE)New York University

Additional Outputs

NIH Award 1R21AI182549-01A1: $466,125 total costs (Boris Reizis, 09/01/2024–08/31/2026): Molecular control of tolerogenic dendritic cell function.

Publication in revision: Adams NM, … Reizis B. Molecular control of the tolerogenic function of dendritic cells.