THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



As inflammasome knowledge expands, so do potential areas for treatment

Pierre Miossec, MD, PhD
Pierre Miossec, MD, PhD

Two researchers who have contributed greatly to understanding the role of the inflammasome and cytokines will share their knowledge Tuesday morning during a Basic Science session.


The Inflammasome & Beyond will take place Tuesday from 7:30 – 8:30 am in Room B309, Building B in the Georgia World Congress Center, with each speaker covering a specific part of the intracellular pathway that controls the activation of inflammation. 


Pierre Miossec, MD, PhD, Professor of Clinical Immunology at the Claude Bernard University in Lyon, France, will start with his presentation on cytokines. Christian Stehlik, PhD, Professor and Director for Pathology Research, Department of Pathology and Laboratory Medicine and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, will then discuss the molecular mechanism that assembles and activates these intracellular pathways that control part of inflammation.


Since the inflammasome is a relatively recent discovery, going back to the early 2000s, the potential clinical applications are very open, Dr. Miossec said. The more common occurence of gout inflammation, for example, goes through the inflammasome, but so do rare genetic defects of the IL-1 and IL-18 pathways.


“The first cytokine to be identified through the inflammasome was IL-1,” Dr. Miossec said. “In fact, when I trained in Dallas, I was the first to describe the presence of bioactive IL-1 at the site of arthritis. So that’s why I feel so honored to be speaking about these cytokines.”


Dr. Miossec’s presentation will include a review of the treatments available that target the IL-1 or IL-18 pathways and a look at potential future treatment options for both pathways, either alone or together. As he was the first to identify the pro-inflammatory and destructive properties of IL-17, that will also be part of Tuesday’s discussion, because during local production of IL-17 at the site of inflammation there a massive activation of caspase 1 and of the inflammasome.


“The inflammasome is sort of a complex factory with different molecules, and the ongoing research is trying to better understand the dynamics, how and where it starts, step by step going through these pathways,” Dr. Miossec said. “And this takes time because at the end you are first defining the molecules and how they interact and then put that in the context of kinetics.”


Dr. Stehlik will discuss the molecular mechanism that assembles and activates the inflammasome. He expects to mostly focus on mechanisms by which excessive inflammasome responses are regulated in macrophages, as in cryopyrinopathy and gout, for example.


While Dr. Stehlik said that his presentation would primarily be of greatest interest to fellow researchers, the crucial role IL-1b plays in rheumatic diseases means that the mechanistic insights into this pathway could be of interest to clinicians. Many attendees will be interested in learning about the unique aspect of the numerous highly similar regulators that evolved to specifically control a key step in inflammasome assembly, and the consequences they have on rheumatic disease pathology.


“Inflammasome responses are crucial for host defense and acute tissue repair responses, but it’s crucial to resolve in a timely manner these acute responses to prevent inflammatory disease,” Dr. Stehlik said. “In humans, several regulators evolved in macrophages to properly regulate and resolve in a timely manner this response, emphasizing this important balanced control to maintain homeostasis.”