Michelle Zuo, Angela A. Wang, Jennifer L. Gommerman
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引用次数: 0
Abstract
Leptomeningeal tertiary lymphoid structures (TLS) have emerged as a relatively common pathological feature of autoimmune disease, including multiple sclerosis (MS) and particularly in people with progressive and nonremitting MS. These ectopic lymphoid aggregates, observed in the leptomeninges adjacent to so-called “Type 3” sub-pial cortical lesions, are associated with more severe gray matter damage and worse clinical outcomes. Mouse models of MS that recapitulate TLS formation in the central nervous system (CNS) have provided critical insights into the mechanisms driving their development and maintenance. In these models of experimental autoimmune encephalomyelitis (EAE) initiation of TLS is facilitated by Th17 cells, which promote chronic inflammation via cytokines such as IL-17 and GM-CSF. The cell surface expression of lymphotoxin-α and lymphotoxin-β heterotrimers (LTαβ) on lymphocytes, including Th17 cells, elaborates the organization of ectopic lymphoid tissues via LTβR signaling on radio-resistant stromal cells and resident fibroblasts. Ultimately a pro-inflammatory environment characterized by cytokines such as IL-17 and GM-CSF promotes the recruitment of neutrophils which produce proteases and chemokines that sustain a pro-inflammatory milieu. Emerging EAE data suggest that disrupting TLS organization or targeting key pathways involved in their maintenance could represent promising strategies for modulating chronic CNS inflammation in MS. Understanding the cellular and molecular mechanisms regulating TLS dynamics is therefore critical for the development of therapies aimed at halting or reversing nonremitting MS disease.
期刊介绍:
Immunological Reviews is a specialized journal that focuses on various aspects of immunological research. It encompasses a wide range of topics, such as clinical immunology, experimental immunology, and investigations related to allergy and the immune system.
The journal follows a unique approach where each volume is dedicated solely to a specific area of immunological research. However, collectively, these volumes aim to offer an extensive and up-to-date overview of the latest advancements in basic immunology and their practical implications in clinical settings.