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Updated: Jan 6, 2026
Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
CARD9 mediates dendritic cell-induced development of Lyn deficiency-associated autoimmune and inflammatory diseases
Jun Ma1, Clare L Abram1, Yongmei Hu1
1Department of Laboratory Medicine and the Program in Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
Insights
Card9 protein regulates immune responses in myeloid cells. Targeting Card9 may suppress autoimmune diseases and colitis by reducing dendritic cell inflammation.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Card9 is an immune adaptor protein in myeloid cells involved in C-type lectin signaling and antifungal immunity.
- Card9 is implicated in autoimmune and inflammatory diseases like rheumatoid arthritis, IgA nephropathy, ankylosing spondylitis, and inflammatory bowel disease (IBD).
- Lyn-deficient mice are susceptible to autoimmunity and IBD, suggesting a link between Lyn and these conditions.
Purpose of the Study:
- To investigate the immunological role of Card9 in the development of autoimmune diseases and IBD using the Lyn-deficient mouse model.
- To elucidate the mechanism by which Card9 influences Lyn-mediated immune regulation.
Main Methods:
- Utilized the Lyn-deficient mouse model to study autoimmune disease and colitis development.
- Investigated the role of Card9 through genetic deletion in both whole mice and dendritic cells specifically.
- Analyzed Toll-like receptor (TLR) signaling pathways in dendritic cells and macrophages.
Main Results:
- Genetic deletion of Card9 reduced spontaneous autoimmune disease and colitis in Lyn-deficient mice.
- Card9 is a crucial component of Lyn-mediated regulation of TLR2 and TLR4 signaling in dendritic cells.
- Amplified signaling through a CD11b-Syk-PKCδ-Card9 pathway in the absence of Lyn led to increased inflammatory cytokine production.
- Dendritic cell-specific deletion of Card9 reversed autoimmune and experimental colitis in Lyn-deficient mice.
Conclusions:
- Card9 plays a vital role in regulating dendritic cell-mediated inflammation in the context of autoimmunity and colitis.
- Targeting Card9 presents a potential therapeutic strategy for suppressing colitis and autoimmunity by modulating dendritic cell function.
Abstract:
CARD9 is an immune adaptor protein in myeloid cells that is involved in C-type lectin signaling and antifungal immunity. CARD9 is implicated in autoimmune and inflammatory-related diseases, such as rheumatoid arthritis, IgA nephropathy, ankylosing spondylitis, and inflammatory bowel disease (IBD). Given that Lyn-deficient (Lyn mice are susceptible to both autoimmunity and IBD, we investigated the immunological role of CARD9 in the development of these diseases using the Lyn mouse model. We found that genetic deletion of CARD9 was sufficient to reduce the development of both spontaneous autoimmune disease as well as DSS- or IL-10 deficiency-associated colitis in Lyn mice. Mechanistically, CARD9 was a vital component of the Lyn-mediated regulation of Toll-like receptor (TLR2 and TLR4) signaling in dendritic cells, but not in macrophages. In the absence of Lyn, signaling through a CD11b-Syk-PKCδ-CARD9 pathway was amplified, leading to increased TLR-induced production of inflammatory cytokines. Dendritic cell-specific deletion of CARD9 reversed the development of autoimmune and experimental colitis observed in dendritic cell-specific, Lyn-deficient mice. These findings suggest that targeting CARD9 may suppress the development of colitis and autoimmunity by reducing dendritic cell-driven inflammation.
