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http://hdl.handle.net/1942/41693
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DC Field | Value | Language |
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dc.contributor.author | Seyedsadr, Maryamsadat | - |
dc.contributor.author | Wang , Yan | - |
dc.contributor.author | Elzoheiry, Manal | - |
dc.contributor.author | Gopal, Sowmya Shree | - |
dc.contributor.author | Jang, Soohwa | - |
dc.contributor.author | DURAN, Gayel | - |
dc.contributor.author | Chervoneva, Inna | - |
dc.contributor.author | Kasimoglou, Ezgi | - |
dc.contributor.author | Wrobel, John A. | - |
dc.contributor.author | Hwang, Daniel | - |
dc.contributor.author | Garifallou, James | - |
dc.contributor.author | Zhang , Xin | - |
dc.contributor.author | Khan, Tabish H. | - |
dc.contributor.author | Lorenz, Ulrike | - |
dc.contributor.author | Su, Maureen | - |
dc.contributor.author | Ting, Jenny P. | - |
dc.contributor.author | BROUX, Bieke | - |
dc.contributor.author | Rostami, Abdolmohamad | - |
dc.contributor.author | Miskin, Dhanashri | - |
dc.contributor.author | Markovic-Plese, Silva | - |
dc.date.accessioned | 2023-11-08T12:37:16Z | - |
dc.date.available | 2023-11-08T12:37:16Z | - |
dc.date.issued | 2023 | - |
dc.date.submitted | 2023-10-26T18:11:44Z | - |
dc.identifier.citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 120 (26) (Art N° e2221007120) | - |
dc.identifier.uri | http://hdl.handle.net/1942/41693 | - |
dc.description.abstract | The objective of this study is to examine IL - 11-induced mechanisms of inflammatory cell migration to the central nervous system (CNS). We report that IL -11 is produced at highest frequency by myeloid cells among the peripheral blood mononuclear cell (PBMC) subsets. Patients with relapsing-remitting multiple sclerosis (RRMS) have an increased frequency of IL -11+ monocytes, IL -11+ and IL -11R+ CD4+ lymphocytes, and IL -11R+ neu-trophils in comparison to matched healthy controls. IL -11+ and granulocyte-macrophage colony-stimulating factor (GM-CSF)+ monocytes, CD4+ lymphocytes, and neutrophils accumulate in the cerebrospinal fluid (CSF). The effect of IL -11 in -vitro stimulation, examined using single -cell RNA sequencing, revealed the highest number of differen-tially expressed genes in classical monocytes, including up-regulated NFKB1, NLRP3, and IL1B. All CD4+ cell subsets had increased expression of S100A8/9 alarmin genes involved in NLRP3 inflammasome activation. In IL -11R+ -sorted cells from the CSF, classical and intermediate monocytes significantly up-regulated the expression of multiple NLRP3 inflammasome-related genes, including complement, IL18, and migratory genes (VEGFA/B) in comparison to blood-derived cells. Therapeutic targeting of this pathway with & alpha;IL- 11 mAb in mice with RR experimental autoimmune encephalomyelitis (EAE) decreased clinical scores, CNS inflammatory infiltrates, and demyelination. & alpha;IL-11 mAb treatment decreased the numbers of NF & kappa;Bp65+, NLRP3+, and IL -1(3+ monocytes in the CNS of mice with EAE. The results suggest that IL-11/IL- 11R signaling in monocytes represents a therapeutic target in RRMS. | - |
dc.description.sponsorship | We thank the study subjects and Dr. Li, Tsygankova, Yang, and Gonzalez for work on experiments and data analysis; Ms. McGuire, Marcello, Boncompagni, Sweeney, and Paglione for clinical data; and Ms. Regan for editorial assistance. The study was supported by NIH 1R01AI131238-01A1 and PA Cure SAP4100083100 grant to S.M.-P. and R01-AI029564 to J.P.T. | - |
dc.language.iso | en | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.rights | 2023 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). Open access | - |
dc.subject.other | multiple sclerosis | - |
dc.subject.other | IL-11 | - |
dc.subject.other | NLRP3 inflammasome | - |
dc.subject.other | EAE | - |
dc.subject.other | monocyte | - |
dc.title | IL-11 induces NLRP3 inflammasome activation in monocytes and inflammatory cell migration to the central nervous system | - |
dc.type | Journal Contribution | - |
dc.identifier.issue | 26 | - |
dc.identifier.volume | 120 | - |
local.format.pages | 11 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | Markovic-Plese, S (corresponding author), Thomas Jefferson Univ, Dept Neurol, Neuroimmunol Div, Philadelphia, PA 19107 USA. | - |
dc.description.notes | silva.markovic-plese@jefferson.edu | - |
local.publisher.place | 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
local.bibliographicCitation.artnr | e2221007120 | - |
dc.identifier.doi | 10.1073/pnas.2221007120 | - |
dc.identifier.isi | 001038062700004 | - |
dc.contributor.orcid | Elzoheiry, Manal/0000-0002-5756-3651; Wrobel, John/0000-0002-5828-9359; | - |
dc.contributor.orcid | Zhang, Xin/0000-0001-7390-4439; Hwang, Daniel/0000-0002-6071-8271 | - |
local.provider.type | wosris | - |
local.description.affiliation | [Seyedsadr, Maryamsadat; Wang, Yan; Elzoheiry, Manal; Gopal, Sowmya Shree; Jang, Soohwa; Kasimoglou, Ezgi; Hwang, Daniel; Rostami, Abdolmohamad; Miskin, Dhanashri; Markovic-Plese, Silva] Thomas Jefferson Univ, Dept Neurol, Neuroimmunol Div, Philadelphia, PA 19107 USA. | - |
local.description.affiliation | [Seyedsadr, Maryamsadat; Su, Maureen] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. | - |
local.description.affiliation | [Duran, Gayel; Broux, Bieke] Hasselt Univ, Biomed Res Inst, Dept Immunol, B-3590 Hasselt, Belgium. | - |
local.description.affiliation | [Chervoneva, Inna] Thomas Jefferson Univ, Dept Pharmacol Biostat Physiol & Canc Biol, Philadelphia, PA 19107 USA. | - |
local.description.affiliation | [Wrobel, John A.] Univ N Carolina, Linberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. | - |
local.description.affiliation | [Garifallou, James] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. | - |
local.description.affiliation | [Zhang, Xin] Duke Univ, Dept Orthoped Surg, Durham, NC 27599 USA. | - |
local.description.affiliation | [Khan, Tabish H.; Lorenz, Ulrike] Washington Univ, Dept Pathol, Divison Lab & Genom Med, Sch Med, St Louis, MO 63110 USA. | - |
local.uhasselt.international | yes | - |
item.fulltext | With Fulltext | - |
item.fullcitation | Seyedsadr, Maryamsadat; Wang , Yan; Elzoheiry, Manal; Gopal, Sowmya Shree; Jang, Soohwa; DURAN, Gayel; Chervoneva, Inna; Kasimoglou, Ezgi; Wrobel, John A.; Hwang, Daniel; Garifallou, James; Zhang , Xin; Khan, Tabish H.; Lorenz, Ulrike; Su, Maureen; Ting, Jenny P.; BROUX, Bieke; Rostami, Abdolmohamad; Miskin, Dhanashri & Markovic-Plese, Silva (2023) IL-11 induces NLRP3 inflammasome activation in monocytes and inflammatory cell migration to the central nervous system. In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 120 (26) (Art N° e2221007120). | - |
item.contributor | Seyedsadr, Maryamsadat | - |
item.contributor | Wang , Yan | - |
item.contributor | Elzoheiry, Manal | - |
item.contributor | Gopal, Sowmya Shree | - |
item.contributor | Jang, Soohwa | - |
item.contributor | DURAN, Gayel | - |
item.contributor | Chervoneva, Inna | - |
item.contributor | Kasimoglou, Ezgi | - |
item.contributor | Wrobel, John A. | - |
item.contributor | Hwang, Daniel | - |
item.contributor | Garifallou, James | - |
item.contributor | Zhang , Xin | - |
item.contributor | Khan, Tabish H. | - |
item.contributor | Lorenz, Ulrike | - |
item.contributor | Su, Maureen | - |
item.contributor | Ting, Jenny P. | - |
item.contributor | BROUX, Bieke | - |
item.contributor | Rostami, Abdolmohamad | - |
item.contributor | Miskin, Dhanashri | - |
item.contributor | Markovic-Plese, Silva | - |
item.accessRights | Open Access | - |
crisitem.journal.issn | 0027-8424 | - |
crisitem.journal.eissn | 1091-6490 | - |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
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pnas.IL-11 paper.pdf | Published version | 3.84 MB | Adobe PDF | View/Open |
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