Trained Immunity and Rheumatoid Arthritis Risk 

Por Vandana Suresh | 7 de abril de 2026 

Why do some individuals at risk for developing rheumatoid arthritis (RA) develop it while others don't? This unpredictability remains one of the most compelling gaps in the quest to stop RA onset. 

To explore this topic, the Arthritis Foundation has awarded a 2025 RA Research Program award to Megan Hanlon, PhD, instructor of medicine at Harvard Medical School. With the Foundation’s support, she will investigate the long-term reprogramming of how a type of immune cell, the monocyte, functions in RA progression. This could one day help predict who will get the disease. 

"What is happening to these monocytes? Are they being trained in some way before they enter the synovium?" asks Dr. Hanlon, referring to the membrane lining the knee joint. "And then, when they finally do enter the synovium, what are the mechanisms that make them poised for these proinflammatory mechanisms? The Arthritis Foundation grant will help us take a step toward understanding RA progression." 

Monocytes are part of the innate immune system and play a role in defending against pathogens, removing dead cells and repairing tissues, among other functions. After being exposed to an inflammatory stimulus, monocytes can be trained, through long-term reprogramming of gene function (without changing the DNA sequence) so that they respond faster and more forcefully to more kinds of threats.  

Recent research shows that endogenous proteins, known as damage-associated molecular patterns (DAMPs), can trigger trained immunity in monocytes. Interestingly, DAMPs are also released in the synovium by fibroblasts, cells that make up synovial tissue. 

"Fibroblasts could be the triggering factor for these monocytes," says Dr. Hanlon. "Trained monocytes traveling through the blood could already be poised to respond to a second trigger. When they get into the inflamed RA synovium, it is that second trigger." 

For her Arthritis Foundation research, she will create a three-dimensional miniature, simplified version of human synovium, called an organoid, which will represent what is happening in the synovium in RA. The organoid will contain fibroblasts from the synovium of RA patients and from healthy individuals who do not have an autoimmune disease but have sustained a knee injury or meniscal tear or have undergone ACL reconstruction surgery. She will then add monocytes from RA patients into the organoid system and monitor changes in them over time. 

In addition, she will use a cutting-edge molecular profiling technique to investigate where the monocytes reside in the joint and whether they are close to fibroblasts. This will help her determine monocyte-fibroblast interaction in people who are at risk of developing RA. If successful, this research could establish a new target for predicting disease onset and preventing early bone loss, ultimately improving the quality of life of RA patients. 

"This is my first award as an independent researcher, so I am thrilled," says Dr. Hanlon. "The Arthritis Foundation's grant comes at a very important stage in my career where I will be merging my expertise in trained immunity with 3D organoid systems to investigate fibroblast and monocyte interaction in the RA synovium closely."