That’s precisely why Elinav’s team embarked on the search for a new inflammasome. In fact, Elinav had a long-standing interest in the topic. During his postdoctoral research, he had identified a new inflammasome that was the first of its kind to be discovered: the NLRP6. It is mainly present in epithelial cells of the gut – the cells making up the gut lining – whereas all five inflammasomes that were known at the time function in immune cells. Each kind of inflammasome is geared toward detecting a different type of threat, ensuring a response that is both rapid and precise. Some inflammasomes, for example, spot DNA in places where it’s not supposed to be – that is, in the cell’s cytoplasm, where it would likely be a sign of a bacterial, viral or fungal infection or a noninfectious stress to the cell.
The search for another new inflammasome began with a mystery. Inflammasomes rely on sensor proteins that belong to the same family but differ somewhat from one another, depending on the kind of threat they identify. One member of the sensing-protein family, called NLRP10, puzzled scientists because it looked like it could lie at the core of an inflammasome – except that it lacked a crucial sensing unit found in its siblings. And a smoke detector missing a sensing component can’t function. Scientists were mystified as to the roles the NLRP10 protein might play in the body.
Elinav’s team, headed by Drs. Danping Zheng, Gayatree Mohapatra and Lara Kern, addressed this question by studying mice, which were found to express the NLRP10 protein in their hearts, skin and the lining of the intestine. By creating genetically engineered mice that lacked NLRP10 in the gut lining cells and comparing them to regular mice in a battery of various experiments, the researchers were able to show that NLRP10 is capable of forming a previously unknown kind of inflammasome. This suggests that despite lacking the classical sensing unit, the NLRP10 protein has other detection capabilities.