Exacerbation of experimental autoimmune encephalomyelitis in mice deficient for DCIR, an inhibitory C-type lectin
Insights
Mice lacking dendritic cell immunoreceptor (DCIR) show worsened experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model. This suggests DCIR is crucial for regulating immune responses and preventing autoimmune diseases.
Area of Science:
- Immunology
- Neuroscience
- Autoimmunity
Background:
- Dendritic cell immunoreceptor (DCIR) is a C-type lectin receptor involved in immune regulation.
- Previous studies indicated DCIR deficiency leads to autoimmune diseases due to dendritic cell expansion.
Purpose of the Study:
- To investigate the role of DCIR in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis.
- To understand DCIR's function in regulating immune responses during autoimmune neuroinflammation.
Main Methods:
- Utilized Dcir knockout (Dcir-/-) mice and wild-type littermates.
- Induced experimental autoimmune encephalomyelitis (EAE) in these mice.
- Analyzed spinal cord pathology, immune cell infiltration (CD11c+ DCs, CD4+ T cells), and lymph node cell proliferation.
Main Results:
- EAE severity was significantly increased in Dcir-/- mice compared to wild-type.
- Dcir-/- mice exhibited severe demyelination in spinal cords.
- Increased infiltration of dendritic cells and CD4+ T cells was observed in the spinal cords of Dcir-/- mice.
- Lymph node cells from Dcir-/- mice showed a higher recall proliferative response.
Conclusions:
- DCIR acts as a critical negative regulator of the immune system.
- Loss of DCIR exacerbates autoimmune neuroinflammation, as evidenced by worsened EAE.
- Dcir-/- mice serve as a valuable model for studying DCIR's role in various autoimmune diseases.
Abstract:
Dendritic cell immunoreceptor (DCIR) is a C-type lectin receptor containing a carbohydrate recognition domain in its extracellular portion and an immunoreceptor tyrosine–based inhibitory motif, which transduces negative signals into cells, in its cytoplasmic portion. Previously, we showed that Dcir(–/–) mice spontaneously develop autoimmune diseases such as enthesitis and sialadenitis due to excess expansion of dendritic cells (DCs), suggesting that DCIR is critically important for the homeostasis of the immune system. In this report, we analyzed the role of DCIR in the development of experimental autoimmune encephalomyelitis (EAE), an autoimmune disease model for multiple sclerosis. We found that EAE was exacerbated in Dcir(–/–) mice associated with severe demyelination of the spinal cords. The number of infiltrated CD11c(+) DCs and CD4(+) T cells into spinal cords was increased in Dcir(–/–) mice. Recall proliferative response of lymph node cells was higher in Dcir(–/–) mice compared with wild-type mice. These observations suggest that DCIR is an important negative regulator of the immune system, and Dcir(–/–) mice should be useful for analyzing the roles of DCIR in an array of autoimmune diseases.
