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Full-Text Articles in Medicine and Health Sciences

The Role Of The Complement System In Chronic Inflammatory Demyelinating Polyneuropathy: Implications For Complement-Targeted Therapies., Luis A Querol, Hans-Peter Hartung, Richard A Lewis, Pieter A Van Doorn, Timothy R Hammond, Nazem Atassi, Miguel Alonso-Alonso, Marinos Dalakas Apr 2022

The Role Of The Complement System In Chronic Inflammatory Demyelinating Polyneuropathy: Implications For Complement-Targeted Therapies., Luis A Querol, Hans-Peter Hartung, Richard A Lewis, Pieter A Van Doorn, Timothy R Hammond, Nazem Atassi, Miguel Alonso-Alonso, Marinos Dalakas

Department of Neurology Faculty Papers

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common, heterogeneous, immune-mediated neuropathy, characterized by predominant demyelination of motor and sensory nerves. CIDP follows a relapsing-remitting or a progressive course and causes substantial disability. The pathogenesis of CIDP involves a complex interplay of multiple aberrant immune responses, creating a pro-inflammatory environment, subsequently inflicting damage on the myelin sheath. Though the exact triggers are unclear, diverse immune mechanisms encompassing cellular and humoral pathways are implicated. The complement system appears to play a role in promoting macrophage-mediated demyelination. Complement deposition in sural nerve biopsies, as well as signs of increased complement activation in …


Challenges And Opportunities For Immunotherapeutic Intervention Against Myeloid Immunosuppression In Glioblastoma, Mark A Exley, Samantha Garcia, Amelia Zellander, Jenny Zilberberg, David W. Andrews Feb 2022

Challenges And Opportunities For Immunotherapeutic Intervention Against Myeloid Immunosuppression In Glioblastoma, Mark A Exley, Samantha Garcia, Amelia Zellander, Jenny Zilberberg, David W. Andrews

Department of Neurosurgery Faculty Papers

Glioblastoma multiforme (GBM), the most common and deadly brain cancer, exemplifies the paradigm that cancers grow with help from an immunosuppressive tumor microenvironment (TME). In general, TME includes a large contribution from various myeloid lineage-derived cell types, including (in the brain) altered pathogenic microglia as well as monocyte-macrophages (Macs), myeloid-derived suppressor cells (MDSC) and dendritic cell (DC) populations. Each can have protective roles, but has, by definition, been coopted by the tumor in patients with progressive disease. However, evidence demonstrates that myeloid immunosuppressive activities can be reversed in different ways, leading to enthusiasm for this therapeutic approach, both alone and …


Pathogenic Tnf-Α Drives Peripheral Nerve Inflammation In An Aire-Deficient Model Of Autoimmunity, Yan Wang, Lily Guo, Xihui Yin, Ethan C Mccarthy, Mandy I Cheng, Aline T Hoang, Ho-Chung Chen, Anushi Y Patel, Denise Allard Trout, Erin Xu, Natalie Yakobian, Willy Hugo, James F Howard, Katherine M Sheu, Alexander Hoffmann, Melissa G Lechner, Maureen A Su Jan 2022

Pathogenic Tnf-Α Drives Peripheral Nerve Inflammation In An Aire-Deficient Model Of Autoimmunity, Yan Wang, Lily Guo, Xihui Yin, Ethan C Mccarthy, Mandy I Cheng, Aline T Hoang, Ho-Chung Chen, Anushi Y Patel, Denise Allard Trout, Erin Xu, Natalie Yakobian, Willy Hugo, James F Howard, Katherine M Sheu, Alexander Hoffmann, Melissa G Lechner, Maureen A Su

Department of Neurology Faculty Papers

Immune cells infiltrate the peripheral nervous system (PNS) after injury and with autoimmunity, but their net effect is divergent. After injury, immune cells are reparative, while in inflammatory neuropathies (e.g., Guillain Barré Syndrome and chronic inflammatory demyelinating polyneuropathy), immune cells are proinflammatory and promote autoimmune demyelination. An understanding of immune cell phenotypes that distinguish these conditions may, therefore, reveal new therapeutic targets for switching immune cells from an inflammatory role to a reparative state. In an autoimmune regulator (Aire)-deficient mouse model of inflammatory neuropathy, we used single-cell RNA sequencing of sciatic nerves to discover a transcriptionally heterogeneous cellular landscape, including …