The macrophage effect, as with T cells, was also mediated by fatty acids, and they’ve found that the fatty acids, oleic acid and linoleic acid, are secreted in higher amounts by adipocytes from people with higher BMIs.
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“What is interesting is that fatty acids have a proinflammatory effect on T cells independently of their saturation grade, which is a bit contrary to the general view that saturated fatty acids would be proinflammatory and unsaturated would be antiinflammatory,” she said. “However, in the case of macrophages, you do see a difference between saturated and unsaturated fatty acids.”
Asked why she thinks those with high BMI have different properties, Dr. Ioan-Facsinay said it’s possible that the factor that mediates the effect (whether it’s fatty acids or something else) is simply secreted in higher amounts in people with a higher BMI.
She was also asked whether these mechanisms might be more prevalent in different types of OA—higher in synovium-driven OA and less so in bone-driven OA. She said she “can very well imagine” differences based on phenotype, but said, “I think it’s difficult to predict because in osteoarthritis you most probably have an interaction between cartilage, bone and synovium.”
Dr. Moody discussed research at Harvard that has been widening the understanding of how T cells function.
For decades, the model for the understanding of T cells has been that they recognize an antigen through the alpha-beta receptor and bind to major histocompatibility complex (MHC) proteins. Building on the earliest studies of lipid antigens from the 1990s, researchers at Harvard in 2004 found that CD1a proteins present a lipopeptide from Mycobacterium tuberculosis.
“You wouldn’t think of this as a usual antigen for a human alpha-beta T cell clone,” Dr. Moody said. “We were very interested how a T cell receptor could recognize a molecule like this.”
Using a sophisticated method to quell autoreactivity, the researchers conducted experiments on a cohort of 17 people with no known disease, finding that all of them showed “demonstrable autoreactivity” to the CD1a protein, suggesting that CD1a autoreactive T cells are a “normal part of the human T cell repertoire,” Dr. Moody said.2 They then set out to determine their immunological function.
They recruited a small group of patients and looked at cytokine profiles. They found that many CD1a-autoreactive T cells homed to skin and produced interleukin 22 (IL-22).3
“We’re actively looking at the question of the general role of CD1a versus MHC in IL-22 response,” Dr. Moody said.