molecule called Tumor Necrosis Factor Alpha (TNF-alpha) is a protein produced by the body's cells. It signals
other cells that then produce additional inflammatory factors.
Previous research suggests that TNF-alpha also induces specialized immune surveillance cells,
called M cells, which both promote inflammation and suppress it. In
other words, TNF-alpha plays a role in the destruction and the healing
of tissues - a double-edged sword.
‘Currently, Tumor Necrosis Factor Alpha (TNF-alpha)-targeted drugs block both receptors, TNFR1 and TNFR2. Newer therapies might be more effective by targeting only TNFR2 as it induces M cells.’
A valuable tip that could help make more effective drugs that block TNF-alpha has been offered by a new research by a team of biomedical scientists at the University of California, Riverside, led by David Lo.
Inflammatory bowel disease is a chronic inflammatory disease of the intestine that includes
Crohn's disease and ulcerative colitis. It is commonly treated with one
of several available biological drugs that block TNF-alpha, but not
everybody is helped by this treatment.
"M cells normally help the immune system detect microbes in the gut,
but in the case of IBD, these may also help bacteria enter tissues and
worsen the inflammation," explained Lo, a distinguished professor of biomedical sciences in the School of Medicine.
His lab now reports that that while there are two receptors for
TNF-alpha, only one receptor, TNFR2, induces M cells. Currently,
TNF-alpha-targeted drugs block both TNFR1 and TNFR2.
"Newer therapies might be more effective by targeting only TNFR2,"
Lo said. "As an analogy, if a soldier knew her enemy was hiding in one
of two caves, she would not debate which cave she should target; she
might blow up both. But if she knows her enemy is in Cave A, then why
would she waste ammunition and risk innocent bystanders by attacking
Cave B as well?"
Study results appear online in the Journal of Crohn's and Colitis
The body's intestinal lining has epithelial cells that form a
barrier so that bacteria in the gut do not pass on into the rest of the
body. During inflammation that occurs in IBD infection, TNF-alpha
triggers an increase in the number of M cells along the colon. The M
cells act like selective gates and serve as a conduit for pathogens to
get across the barrier and into the body.
"The question is if you have more M cells, do you have better immune
surveillance or do you have more bacteria getting across the barrier?"
Lo said. "From a therapeutic point of view we might want to tamp M-cell
production down just enough so that the immune system can do its job
without having a whole lot of bacteria pass into the body from inside
Lo explained why not everybody with IBD benefits from anti-TNF drugs.
"These drugs target both TNRF-alpha receptors: TNFR1 and TNFR2," he
said. "But our research identifies a distinct inflammation-inducible
M-cell population that is dependent on TNFR2 signaling, but not TNFR1.
If too many M cells are being produced, then the anti-TNF drug being
used is not sufficiently blocking TNRF2, which induces the M cells, and
is instead blocking the other receptor. If we understand why there are
two receptors, then instead of drugs doing a global blockade, more
focused therapeutic approaches could target only one of the receptors,
resulting in a more efficient suppression of the inflammation we see in
An ongoing challenge for biomedical scientists doing IBD research is
gaining a full understanding of the role M cells play in chronic
inflammation. It remains unclear whether M cells help promote continuing
inflammation or whether they are critical to initiating
"Knowing these roles should lead to more specifically targeted
therapies that will promote the regulation and resolution of chronic
intestinal inflammation," Lo said.