Newly identified cells in fascia may drive exaggerated inflammation in the skin


Microscope image of skin fascia showing TIFFs labeled in green. Selected TIFFs are labeled in pink to visualize their star-like shape. Photo courtesey: Rosenblum Lab

A newly discovered type of skin cell may explain how inflammation to the skin early in life may prime an individual for inflammatory skin disease.

The cells, which researchers have named ‘TIFFs’ (Th2-interacting fascial fibroblasts), were discovered during an investigation of the effects of a set of actions known to evoke an immune response in mice. When the team removed a class of cells known to suppress the immune system, they observed the proliferation of the newly identified cells, which seemed to be acting as a shelter for pathogenic immune cells not normally seen in skin tissues.


The findings were published online in Nature (Oct. 27, 2021).


“We had to knock out one cell population to see that they were controlling the growth and capacity of these other, unknown cells,” said the study’s principal investigator Dr. Michael Rosenblum, noting in a press release that the new cells became apparent only in the tissue that had been exposed to inflammatory triggers. “What normally would be a deserted island on the skin was now inhabited by all these strangers,” he said.

The investigators observed that when the skin lacking regulatory cells is subjected to inflammatory triggers, the population of TIFFs expanded rapidly. These TIFFs then accumulate Th2 immune cells. Later in life, when even a small insult to the skin presents itself again, the TIFFs release the Th2 cells which in turn cause inflammation.

“All you need to do is push the immune system just a little bit, with a wound or with stress, to unleash all the pathogenic cells living in these TIFFs and create an exaggerated inflammatory response,” Dr. Rosenblum said.

That exaggerated response, the researchers hypothesize, may manifest as the creation of fibroses in the fascia, the driving force behind inflammatory skin diseases such as scleroderma.


To confirm their findings the researchers looked at skin samples taken from humans with eosinophilic fasciitis (EF) and from healthy controls. While TIFFs were found in all the human samples, there were many more of them in the fascia from the EF samples.

Dr. Rosenblum noted that TIFFs appear to be present in every organ of the body, typically found in the fascia that surrounds our major organs and serve a role in maintaining structure.

He postulated that TIFFs might have evolved as a sort of emergency brigade in case of injury, able to jump-start repair in the case of internal injury.

“In patients with scleroderma or other fibrosing diseases like EF, that repair program may be kind of co-opted, resulting in this chronic wound-healing response,” said Dr. Rosenblum. “If we can understand the biology of these cells, we can come in with drugs that revert them back to what they’re supposed to be doing.”

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