An immune link between the gut and the skin in eczema

New research led by Raif Geha at Children's Hospital Boston has revealed how the immune system connects the gut to the skin, and thus how food allergies may affect the skin.

The connection is made by helper T cells. Geha and his team were investigating, in mice, how it is that an allergic reaction that the body has to a food--and we all know that the usual way that food enters the body is when we eat it--can manifest as an eczema-type reaction when the food is rubbed on the skin. Not eaten; rubbed on the skin.

The authors of the paper claim that this is a common occurrence but I beg to differ. I've never heard of it. But they put a lot of work (and taxpayers' money) into their experiments, and their results are intriguing.

Helper T cells are white blood cells whose job it is to detect foreign material in the body, and when it's detected, to stimulate B cells to produce antibodies. What I didn't know was that there are distinct populations of T cells, determined by molecules embedded in their outer membranes, which home in on different regions of the body. Some go to the gut; some to the skin; presumably, some to the lungs, etc. What happens is that the molecules in their membranes will bind specifically to "adhesion molecules" that are found in these different regions. A T cell that homes to the gut will stick to the adhesion molecules in the gut but not the skin.

And Geha and colleagues find that T cells that originally home to the gut can be reprogrammed to head to the skin instead. They immunized mice with the egg protein ovalbumin, and then later observed what happened when ovalbumin was applied to the skin of the mice. Normal mice developed eczema-like inflammation at that spot. Mice that had been genetically engineered with T cells that did not have the skin-homing surface molecule CCR4 did not show signs of eczema. In a truly gruelling series of experiments carried out late at night by grad student slaves, the authors showed that the initial immunization generated a bunch of gut T cells specifically programmed to hunt down ovalbumin; the body then modified these T cells to head to the skin. The reprogramming takes place in the lymph nodes.

I find this fascinating; I didn't know there was such a pathway. It could be that (in the way distant future) someone will develop a way to treat eczema patients with well-defined food allergies, and in these patients prevent the food-antigen-specific T cells from homing to the skin.

The research raises one huge question for me, though. Most eczema related to food allergy does not occur because we rub food on our skin. (At least, I know that I'm allergic to parmesan, but I sure as hell don't go rubbing it on the backs of my knees.) So what is going on to connect the gut to the skin and cause inflammation in the majority of eczema patients?