Dr. Sanja Arandjelovic has been studying inflammation and arthritis for a while – specifically, how a gene called ELMO1 is related toarthritis symptoms在老鼠身上。2010年，关节炎基金会授予Arandjelovic博士Philip S. Maaram Esq。Research (Planned Giving) 3-year grant for a project that studied cell enzymes related to joint inflammation inrheumatoid arthritis (RA)在老鼠身上。
During this study, Dr. Arandjelovic worked with Dr. Kodi Ravichandran and his research team at theUniversity of Virginiaon a related project, examining the process ofjoint inflammationin RA. Their work may provide clues to why the pain flare-ups associated with RA occur – and lead to new treatments.
RA causes chronic and progressive joint destruction due to uncontrolled inflammation. When the body senses inflammation in the joint, specialized immune cells, called neutrophils, rush into the soft tissue lining the joint to fight infection. But in this process, they can damage the tissue and increase cell death. Inefficient clearance of these damaged cells further fuels chronic inflammation and contributes to autoimmunity.
So, how does ELMO1 fit in?The ELMO1 gene codes for a protein called Engulfment and Cell Motility Protein 1 (ELMO1 protein). ELMO1 has two main functions: It is involved in the anti-inflammatory process (clearing damaged cells), but it also promotes cell migration.
The research team decided to delete the ELMO1 gene from the mice, to see how the loss of ELMO1 protein would influence disease severity in RA models. Deleting a gene can cause unexpected side effects. In this case, deleting ELMO1 might cause the immune system to work less effectively and increase inflammation due to inefficient clearance of damaged cells. Surprisingly, the team discovered that deleting ELMO1 didn’t inhibit the immune system at all. Instead, deleting the ELMO1 gene from neutrophils alleviatedRA symptomsin mice, blocking their migration into the joints and reducing tissue damage.
这一在小鼠身上的基本发现为人类关节炎的转化研究提供了巨大的潜力。“我们计划继续研究ELMO1在关节炎中起作用的机制——为什么它只针对关节而不是其他组织，”Arandjelovic博士说。“开发针对ELMO1功能的治疗化合物有很大的潜力。”
“We’ve discovered connections between this gene and other inflammatory diseases,” she continues. The team has found similarities in a gene variation, called single nucleotide polymorphisms (SNPs – pronounced “snips”) in one region of the ELMO1 gene. This variation is common to not only RA, but also to other autoimmune diseases, such as diabetes, psoriasis and Celiac disease. “Identifying these particular SNPs could potentially be used in simple blood tests, to detect an elevated risk for developing one of the conditions,” she says.
You can read more about the findings of this study in the February edition ofNature Immunology.
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