Sea squirts flip immunity switch

UC SANTA BARBARA (US) — Preventing rejection of transplanted organs and bone marrow may lie with the tiny sea squirt, a small organism with an incredible sense of self.

An average of 20 registered patients die every day waiting for transplants, due to the shortage of matching donor organs. More than 110,000 people are currently waiting for organ transplants in the U.S. alone. Currently, only one in 20,000 donors is a match for a patient waiting for a transplant.

Researchers hope to understand how it might be possible to “tune” the body’s immune response in order to dial down the rejection of a donated organ. Studying cellular responses in simple organisms may also eventually help with autoimmune diseases––those in which the body mistakenly attacks itself.

“Right now, when you get a transplant, you’re usually on immunosuppressives your whole life,” says Anthony De Tomaso, assistant professor of biology at the University of California, Santa Barbara.


“And that’s like sort of kicking your immune system in the teeth. What if we could raise the threshold of when you would respond, instead of just shutting the whole system off?”

De Tomaso was involved in identifying the gene controlling the choice between fusion and rejection in the sea squirt when he was a postdoctoral fellow at Stanford University.

The sea squirt is a modern day descendant of the vertebrate ancestor, the group to which humans belong. Known as a tunicate because of its covering, or “tunic,” it begins life as a swimming tadpole with a primitive backbone, nerves, and musculature similar to all vertebrates, but soon transforms into stationary creatures.

Tunicates latch onto intertidal surfaces and look like flat flowers––with each “petal” being a separate, but genetically identical, body.

When one sea squirt lands next to another cells in the sea squirt’s fingerlike edges, or “ampullae,” recognize the neighboring sea squirt as “self” or “non-self.” When the other sea squirt is related, then the two colonies fuse; otherwise, they reject each other.

For the new study, De Tomaso researched  how the signals on the surface of the sea squirt’s cells get translated inside the circuitry of the cell, where the final decision about acceptance or rejection is made.

The latest results are published online in the journal Immunity.

“In the case of Botryllus, what we found is that we have the same kind of integration that goes on in humans, but instead of having a multiple, very complex set of inputs coming in, we only have two,” DeTomaso says.

“We have also found that we can manipulate each one independently, so we know that somehow they are put together and the two inputs are integrated, and a decision is made about how to respond.”

De Tomaso decided to work on Botryllus because it has a unique way to answer a very complicated question. He hopes to understand the process of rejection or acceptance.

“If we could manipulate that process,” says Tomaso, “then we could basically teach the immune system to simply ignore certain things. We could say, ‘Just don’t respond to this. We’re going to transfer this bone marrow, just don’t kill this bone marrow.’ Bone marrow could get in and start making new blood, and it would be fine. To me, that’s the most exciting thing long-term for the work.”

Researchers from Stanford University and Washington University contributed to the study.

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