People living with multiple sclerosis (MS) experience episodic CNS white matter lesions instigated by autoreactive T cells. With age, patients with MS show evidence of gray matter demyelination and experience devastating nonremitting symptomology. What drives progression is unclear and studying this has been hampered by the lack of suitable animal models. Here, we show that passive experimental autoimmune encephalomyelitis (EAE) induced by an adoptive transfer of young Th17 cells induced a nonremitting clinical phenotype that was associated with persistent leptomeningeal inflammation and cortical pathology in old, but not young, SJL/J mice. Although the quantity and quality of T cells did not differ in the brains of old versus young EAE mice, an increase in neutrophils and a decrease in B cells were observed in the brains of old mice. Neutrophils were also found in the leptomeninges of a subset of progressive MS patient brains that showed evidence of leptomeningeal inflammation and subpial cortical demyelination. Taken together, our data show that while Th17 cells initiate CNS inflammation, subsequent clinical symptoms and gray matter pathology are dictated by age and associated with other immune cells, such as neutrophils.
Michelle Zuo, Naomi M. Fettig, Louis-Philippe Bernier, Elisabeth Pössnecker, Shoshana Spring, Annie Pu, Xianjie I. Ma, Dennis S.W. Lee, Lesley A. Ward, Anshu Sharma, Jens Kuhle, John G. Sled, Anne-Katrin Pröbstel, Brian A. MacVicar, Lisa C. Osborne, Jennifer L. Gommerman, Valeria Ramaglia
Usage data is cumulative from January 2024 through January 2025.
Usage | JCI | PMC |
---|---|---|
Text version | 1,564 | 374 |
163 | 109 | |
Figure | 517 | 19 |
Supplemental data | 94 | 23 |
Citation downloads | 64 | 0 |
Totals | 2,402 | 525 |
Total Views | 2,927 |
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.