Usage Information
Citation Information: JCI Insight. 2025;10(13):e188843. https://doi.org/10.1172/jci.insight.188843.
Abstract
Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy, but their use is limited by the development of autoimmunity in healthy tissues as a side effect of treatment. Such immune-related adverse events (IrAE) contribute to hospitalizations, cancer treatment interruption, and even premature death. ICI-induced autoimmune diabetes mellitus (ICI-T1DM) is a life-threatening IrAE that presents with rapid pancreatic β-islet cell destruction leading to hyperglycemia and life-long insulin dependence. While prior reports have focused on CD8+ T cells, the role for CD4+ T cells in ICI-T1DM is less understood. We identify expansion of CD4+ T follicular helper (Tfh) cells expressing IL-21 and IFN-γ as a hallmark of ICI-T1DM. Furthermore, we show that both IL-21 and IFN-γ are critical cytokines for autoimmune attack in ICI-T1DM. Because IL-21 and IFN-γ both signal through JAK/STAT pathways, we reasoned that JAK inhibitors (JAKi) may protect against ICI-T1DM. Indeed, JAKi provide robust in vivo protection against ICI-T1DM in a mouse model that is associated with decreased islet-infiltrating Tfh cells. Moreover, JAKi therapy impaired Tfh cell differentiation in patients with ICI-T1DM. These studies highlight CD4+ Tfh cells as underrecognized but critical mediators of ICI-T1DM that may be targeted with JAKi to prevent this grave IrAE.
Authors
Nicole L. Huang, Jessica G. Ortega, Kyleigh Kimbrell, Joah Lee, Lauren N. Scott, Esther M. Peluso, Sarah J. Wang, Ellie Y. Kao, Kristy Kim, Jarod Olay, Jaden N. Nguyen, Zoe Quandt, Trevor E. Angell, Maureen A. Su, Melissa G. Lechner
Usage data is cumulative from July 2025 through December 2025.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 2,704 | 175 |
| 461 | 58 | |
| Figure | 309 | 4 |
| Supplemental data | 108 | 3 |
| Citation downloads | 128 | 0 |
| Totals | 3,710 | 240 |
| Total Views | 3,950 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
