While some Th17 immune cells maintain healthy tissue, others can turn harmful and drive autoimmune disease.

Ana Anderson, PhD

Vijay Kuchroo, DVM, PhD

In two new, related studies, researchers at the Gene Lay Institute of Mass General Brigham and Harvard, the Broad Institute of MIT and Harvard, and collaborating institutions explored what keeps healthy Th17 cells stable and what flips them into a harmful state.

Until now, these mechanisms haven’t been fully understood.

The researchers discovered that certain signals in Th17 cells create a self-reinforcing loop in which the cells make and respond to their own anti-inflammatory steroid hormones, called glucocorticoids. This self-regulating system keeps them from becoming inflammatory Th17 cells, which have weaker hormone signaling and respond less to steroids.

They also probed the role of IL-23, an immune signal, in pushing Th17 cells from healthy to harmful. When IL-23 signaling is active, there’s a double‑whammy effect: Specific proteins inside Th17 cells help switch on genes that drive inflammation, while IL-23 signaling also shuts down the cell’s built-in anti-inflammatory system, making the cells overactive.

Dandan Yang, PhD

These findings help explain what may underlie steroid resistance in autoimmune disease and suggest that blocking IL-23—and restoring Th17 cells’ self-regulating processes—could improve treatment responses.

Study 1: Published in Immunity on June 12, 2026 | Read the paper:

“Interleukin 23 promotes a pro-inflammatory Th17 cell state by stabilizing RORγt and suppressing glucocorticoid receptor activity”

Study 2: Published in Immunity on June 12, 2026 | Read the paper:

“A cell-intrinsic glucocorticoid biosynthesis and sensing circuit maintains a homeostatic Th17 cell state”

Summary reviewed by: Dandan Yang, PhD, Ana Anderson, PhD, and Vijay Kuchroo, DVM, PhD