Regulatory interaction pinpointed that could pave new pathway for treating inflammatory diseases

Immune cells are integral to tamping down inflammatory responses, and one such cell central to autoimmune diseases is the dendritic cell. Now, researchers in Japan have found a molecule important to the activity of the receptor that regulates dendritic cells and is likely involved in the development of arthritis and other autoimmune diseases.

Researchers at Tokyo University of Science found that certain parts of glycoproteins interact with the regulator, known as the dendritic cell immunoreceptor, or DCIR. Previously, little had been detailed about the molecules that interact with DCIR to help referee inflammatory responses, the researchers published in the Journal of Experimental Medicine. 

The team found that cells lacking enough DCIR had a significant increase in the expression of genes associated with a process that contributes to bone loss, known as osteoclastogenesis. They also found that DCIR is likely an inhibitor of this process, since the regulator suppresses the differentiation of osteoclasts, which are involved in bone degradation. 

The specific ligand, or a molecule that binds to a cell receptor, that interacts with DCIR was found to have an impact on osteoclastogenesis as well. Asialo-biantennary N-glycan, or NA2 for short, was found to suppress osteoclast differentiation from wild-type bone marrow-derived macrophages but didn't differentiate from cells lacking enough DCIR. That emphasized NA2's role as a ligand of DCIR that helps tamp down osteoclastogenesis, the team said.

The researchers gave mice that were modeling autoimmune diseases a treatment that ramped up the exposure of NA2. The treatment, using an enzyme that removes certain sialic acid residues from N-glycan, was able to further hamper arthritis, encephalomyelitis and other autoimmune diseases. 

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The work of DCIR and NA2 teaming up to inhibit autoimmune diseases resulted from the suppression of dendritic cells' ability to present antigens and a lowering of activity of other immune cells core to inflammation. 

These findings add to the team's previous work that found mice deficient in DCIR wound up developing arthritis and metabolic bone disorders.

Now, having found the interaction between DCIR and NA2, the researchers believe this regulatory channel can be a path forward for new therapeutics targeting immune and bone metabolic diseases.