Ah, the pancreas. That organ behind the stomach that's always been the target of angst and anger for us PWDs (people with diabetes). We bemoan why it went on permanent vacation and daydream about kick-starting it...
But all of our complaining might be for naught. Turns out there might be an even bigger, badder enemy of healthy blood sugars: the thymus!
... the who??
Let me tell you a little about this other gland:
The Thymus Unveiled
The thymus is sort of a forgotten player in the Musical of the Malfunctioning Pancreas. It is a tiny butterfly-shaped gland that sits in the middle of your lung. During childhood, it's responsible for creating your immune system, but around puberty the thymus starts to shrink and degenerate so it gets very little mention in adulthood. Because the thymus creates your immune system, it's the main catalyst for autoimmune diseases, including diabetes!
In type 1 diabetes, your T-lympocytes (commonly known as T-cells) are programmed by educator-cells in the thymus to recognize what is part of you and what isn't. Normal thymuses actually use itty-bitty amounts of insulin to show T-cells what insulin is. But for type 1 PWDs, that step goes missing. Your T-cells are trained to look for foreign cells -- like the seasonal flu making its rounds right now -- and without that exposure to insulin, your beta cells look the same as a virus.
"You can imagine the good immune cells as part of an army, ready to fight off potential microbial invaders, the suppressor cells as military police, and the bad cells as rogue soldiers that can betray their country any time if uncontrolled," explains Dr. Remi Creusot, a researcher at Columbia University Medical Center.
Unfortunately, Dr. Creusot says the suppressor cells also aren't trained to know that rogue beta cell-killing T-cells are bad, so they are left alone.
The problem in type 1 diabetes is that the thymus wrongly teaches your T-cells that your pancreas' beta cells are a foreign body. Researchers aren't entirely sure why T-cells are mis-educated, but they think a genetic component might be at issue. In any event, these T-cells take off into the body, thinking beta cells are the equivalent to the flu, so they whack 'em off.
Even if researchers were to give you brand-spanking new islet cells (either from an islet cell transplantation, stem cells, or xenotransplantation), your body would still seek out and destroy any beta cell it found -- even if it matched you perfectly. In fact, research has shown that the autoimmunity still affects PWDs who have undergone an islet cell transplant, despite the fact they are taking immuno-suppressant drugs. This has led researchers to believe that the underlying autoimmunity must be addressed if there is any hope for a cure.
Reprogramming the Immune System
At a recent research update hosted by Columbia University Medical Center, I learned about two researchers who are working on different methods to stop the autoimmunity. They are Dr. Creusot and Dr. Hans Snoeck, both working on ways to stop the creation of rogue cells. Their separate lines of research alternatively aim to make sure any rogue cells created are summarily destroyed by suppressor cells.
To reverse autoimmunity, researchers are actually looking in two places: the thymus, which creates the T-cells; and the lymph nodes, which is where the T-cells live once they're released from the thymus.
"One can intervene at two levels," Dr. Creusot says. "First, restore the optimal function of thymic educator cells and second, enhance the capability of lymph node educator cells to promote tolerance or neutralize rogue immune cells. Although each intervention can certainly help a great deal, both applied together would probably prevent autoimmunity."
Waging war against the mutineers! Sounds like the next Summer Blockbuster...
Using gene therapy, Dr. Creusot plans to tackle step No. 2: "My approach is to use particular immune cells, normally involved in starting immune responses, and turning them into educator cells capable of going preferentially to the pancreatic lymph nodes and deal with this group of rogue cells that are about to go invade their targets in the pancreatic islets."
Dr. Creusot's method takes out the rogue cells that our thymus has already created, but it of course it must hone in on T-cells attacking beta cells, rather than taking out the entire immune system (!)
Regenerating a Thymus
While Dr. Cereusot and his team are working on identifying the genes needed to express insulin in the thymus (and other parts of the immune system, like the lymph nodes), Dr. Snoeck is working on making us an all-new thymus from stem cells. Why do we need a new thymus? And why would we want to regrow our clearly dysfunctional thymus?
"We cannot grow and manipulate cells of a adult thymus in the lab, or at least, that appears very problematic," Dr. Snoeck explains, because the thymus shrinks as you get older. Even at the tender age of 27, my thymus is but a shadow of its former self. That means doing any kind of modification to it is pretty unlikely.
"'Resetting' the immune system would therefore require a new thymus, and likely removal of the remaining old thymus." He adds that the best way to program your own immune system is to have the thymus come from your own cells, thus Dr. Snoeck's research is focused on creating a new thymus out of your own stem cells.
Still, wouldn't creating a thymus from your own stem cells just repeat the problem? Our cells were what created this whole mess in the first place, right?!
Dr. Snoeck's research is also focused on re-training educator cells in the thymus to recognize insulin. He says that this is possible with a large, new thymus. And in theory, it would allow the same kind of re-education of the lymph nodes that could be done in the thymus.
"There is always a chance that some new rogue T-cells can be made," Dr. Creusot says. "Having new educator cells in the thymus and/or in the lymph nodes is important to block rogue T-cells if you want to protect your transplanted islets." The new thymus would also be responsible for creating that "military police" of suppressor cells, ready to take out any rogue cells that undoubtedly will escape the thymus.
Despite the shrinking adult thymus, new T-cells are still made all throughout adulthood, which is why it's important to create educator cells that know how to create beta cell-friendly T-cells.
This early stage research, as you can imagine, is currently being done in mice. But it's just one more example of all the various avenues being explored to help find a cure for this complicated and confounding disease!
The good news here is that if and when we do find a way to transplant enough new cells into every PWD, we won't have to worry about diabetes coming back -- because the cells will be re-trained to do what healthy cells ought to do.