University breakthrough in fight against Crohns disease

University breakthrough in fight against Crohns disease
http://www.irishtimes.com/news/health/university-breakthrough-in-fight-against-crohns-disease-1.1477630

Very much appreciate you posting the link. It seems that this is going to be more of a diagnostic tool than a treatment.

This is interesting. I looked at the study abstract and since I couldn't understand it, I asked my
daughter who is working on a PhD in immunology if she could explain it to me in terms that
I could understand. This is her reply:



" There are a bunch of receptors on cells that recognize microbes (or sometimes even host products that signal there is an infection), these are called pattern recognition receptors (PRRs). The most famous ones are TLRs (you've probably heard me talk about them), but the other ones are Nod-like receptors (NLRs), which includes Nod2, and mutations in this one have been linked to Crohn's disease (and since NLRs recognize microbes, that's why many people think Crohn's disease is due to not being able to recognize and respond to microbes properly).



There is a process called ubiquitination, which basically marks proteins and other products for degradation or sometimes for moving them to another location in the cell (there are other functions, but these are the most common results). I don't know the genes/proteins they are looking at in this paper, but basically they were using mice that do not have a functional protein (Pellino3) for doing ubiquitination. They found that colitis in these mice was worse, and they also checked in CD patients and found they had lower levels of Pellino3.




Then they looked to see what this protein actually does, and it is responsible for adding ubiquitin to RIP2. If Pellino3 isn't around, then RIP2 isn't ubiquinated, and this meant that there was less NF-kB and MAPK activation (these are major pathways that respond to microbial infection and also are responsible for creating lots of inflammatory products). This is interesting, because most people want to reduce inflammation in CD, but this study seems to indicate that less inflammation (because NF-kB and MAPKs weren't as activated) actually made the disease worse. There are lots of functions of NF-kB and the MAPKs beside just creating inflammation, but it's still really interesting (which is probably why this is in Nature Immunology, arguably the best immunology journal). "

But again, it's just comforting to some extent to know that there are people out there who have dedicated their lives to helping us.