title: IL-11 Induces Th17 Cell Responses in Patients with Early Relapsing-Remitting Multiple Sclerosis.
abstract: Clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) is the earliest clinically evident phase of the disease, which may provide valuable insight into the molecular mechanisms of the initiation of the autoimmune response in MS. Our results introduce IL-11 as a new cytokine that plays a role in the autoimmune response in the early phase of the disease. IL-11 is the highest upregulated cytokine in the sera and cerebrospinal fluid from CIS patients, which is also increased in patients with clinically definitive relapsing-remitting MS in comparison with healthy control subjects. Serum IL-11 levels are significantly increased during clinical exacerbations in comparison with remissions in the same patients. CD4(+) cells represent a predominant cell source of IL-11 in the peripheral circulation, and the percentage of IL-11(+)CD4(+) cells is significantly increased in CIS patients in comparison with healthy control subjects. Furthermore, we have identified IL-11 as a new Th17-promoting cytokine, because it induces a differentiation of naive CD4(+) T cells into Th17 cells, as well as expansion of Th17 memory cells. Because the Th17 cytokines IL-17F, IL-21 and TNF-α, and TGF-β induce differentiation of naive cells in the IL-11-secreting CD4(+) cells, we propose that cross-talk between IL-11(+)CD4(+) and Th17 cells may play a role in the inflammatory response in relapsing-remitting MS.
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Yazhong
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Manisha
authors.initials: M
authors.lastname: Chopra
authors.affiliation: Department of Neurology, Clinical Center Serbia, Belgrade 11129, Serbia;
authors.forename: Irena
authors.initials: I
authors.lastname: Dujmovic-Basuroski
authors.affiliation: Center for Bioinformatics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; and.
authors.forename: Jianping
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Yunan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Neurology, Clinical Center Serbia, Belgrade 11129, Serbia;
authors.forename: Jelena
authors.initials: J
authors.lastname: Drulovic
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 markovic@email.unc.edu.
authors.forename: Silva
authors.initials: S
authors.lastname: Markovic-Plese
mesh_terms: D000328:Adult; D015551:Autoimmunity / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D017370:Interleukin-11 / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D020381:Interleukin-17 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000098546:Interleukin-21
chemical_list: C508611:IL11 protein, human; C440021:IL17F protein, human; D017370:Interleukin-11; D020381:Interleukin-17; D007378:Interleukins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000098546:Interleukin-21