Neuroinflammatory diseases, such as multiple sclerosis, are characterized by invasion of the brain by autoreactive T cells. The mechanism for how T cells acquire their encephalitogenic phenotype and trigger disease remains, however, unclear. The existence of lymphatic vessels in the meninges indicates a relevant link between the CNS and peripheral immune system, perhaps affecting autoimmunity. Here we demonstrate that meningeal lymphatics fulfill two critical criteria: they assist in the drainage of cerebrospinal fluid components and enable immune cells to enter draining lymph nodes in a CCR7-dependent manner. Unlike other tissues, meningeal lymphatic endothelial cells do not undergo expansion during inflammation, and they express a unique transcriptional signature. Notably, the ablation of meningeal lymphatics diminishes pathology and reduces the inflammatory response of brain-reactive T cells during an animal model of multiple sclerosis. Our findings demonstrate that meningeal lymphatics govern inflammatory processes and immune surveillance of the CNS and pose a valuable target for therapeutic intervention.
Discovery of the meningeal lymphatic vessels in the brain meninges (coverings of the brain) led to the hypothesis that they carry macromolecules and immune cells from cerebrospinal fluid (CSF) to cervical lymph nodes (cLN). Our new findings suggest that the lymphatic system controls immune responses through guiding antigen-presenting cells, such as dendritic cells (DC) from the meninges to draining lymph nodes. By using surgical and pharmacological methods to interfere with meningeal lymphatic vessels, we found lymphatics to serve as a major conduit by which DC leave the meninges, traffic to cLN and promote the generation of antigen-specific T cells. Inflammation-induced migration of DC is primarily regulated through a CC-chemokine receptor 7 (CCR7) dependent pathway. Co-injection of equal parts of differentially labeled CCR7-deficient and wild-type (WT) DCs into the CSF of the brain did allow translocation of CCR7-competent DC into the T cell zone of the draining lymph nodes but not CCR7−/− DC. Subsequently, antigenic stimulation by CCR7−/− DC did not induce a T cells response in the cLN, whereas WT DC enforced the majority of antigen-specific T cells to proliferate and increase their effective trafficking through integrin expression. To gain insights into how T cell responses are elicited when the meninges are infected with a virus, we currently set out to understand the lymphatics function in a mouse model of virus-induced meningitis. Injection of Lymphocytic choriomeningitis virus into the CSF induces rapid, uniform and fatal inflammation that is dependent on the generation of viral specific CD8+ T cells and potentially the exit of migratory DC through meningeal lymphatic vessels.
issue expander-based reconstruction is the most common approach for two-stage breast reconstruction in the United States. 1,2 Tissue expanders (TEs) were first developed by Radovan in the 1980s to expand the soft-tissue envelope for postmastectomy breast reconstruction. 3 Maxwell Background: With ongoing investigations of the impact of device texturing on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL), studies have begun comparing complication profiles of tissue expanders. However, there is a paucity of timing and severity data of complications. The aim of this study was to provide a comparative survival analysis of postoperative complications between smooth (STEs) and textured tissue expanders (TTEs) in breast reconstruction. Methods: A single-institution experience with tissue expander breast reconstruction was reviewed for complications up to 1 year after second-stage reconstruction from 2014 to 2020. Demographics, comorbidities, operation-related variables, and complications were evaluated. Kaplan-Meier curves, Cox proportional hazard models, and a consensus-based ordinal logistic regression model were used to compare complication profiles. Results: Of 919 total patients, 600 (65.3%) received TTEs and 319 (34.7%) received STEs. There was increased risk of infection (P < 0.0001), seroma (P = 0.046), expander malposition (P < 0.0001), and wound dehiscence (P = 0.019) in STEs compared with TTEs. However, there was also a decreased risk of capsular contracture (P = 0.005) in STEs compared with TTEs. Failure of breast reconstruction (P < 0.001) and wound dehiscence (P = 0.018) occurred significantly earlier in STEs compared with TTEs. Predictors for significantly higher severity complications included the following: smooth tissue expander use (P = 0.007), shorter time to complication (P < 0.0001), higher body mass index (P = 0.005), smoking history (P = 0.025), and nipple-sparing mastectomy (P = 0.012). Conclusions: Differences in the timing and severity of complications contribute to the safety profiles of tissue expanders. STEs are associated with increased odds of higher severity and earlier complications. Therefore, tissue expander selection may depend on underlying risk factors and severity predictors. (Plast.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.