B7-H1 Selectively Controls TH17 Differentiation and Central Nervous System Autoimmunity via a Novel Non-PD-1-Mediated Pathway
Publikation: Beiträge in Zeitschriften › Zeitschriftenaufsätze › Forschung › begutachtet
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B7-H1 Selectively Controls TH17 Differentiation and Central Nervous System Autoimmunity via a Novel Non-PD-1-Mediated Pathway. / Herold, Martin; Posevitz, Vilmos; Chudyka, Daria et al.
in: Journal of immunology (Baltimore, Md. : 1950), Jahrgang 195, Nr. 8, 15.10.2015, S. 3584-3595.Publikation: Beiträge in Zeitschriften › Zeitschriftenaufsätze › Forschung › begutachtet
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TY - JOUR
T1 - B7-H1 Selectively Controls TH17 Differentiation and Central Nervous System Autoimmunity via a Novel Non-PD-1-Mediated Pathway
AU - Herold, Martin
AU - Posevitz, Vilmos
AU - Chudyka, Daria
AU - Hucke, Stephanie
AU - Groß, Catharina
AU - Kurth, Frank
AU - Leder, Christoph
AU - Loser, Karin
AU - Kurts, Christian
AU - Knolle, Percy
AU - Klotz, Luisa
AU - Wiendl, Heinz
N1 - Copyright © 2015 by The American Association of Immunologists, Inc.
PY - 2015/10/15
Y1 - 2015/10/15
N2 - It is currently acknowledged that T H17 cells are critically involved in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). In this article, we demonstrate that signals delivered by the coinhibitory molecule B7-homologue 1 (B7-H1) via a B7-homologue 1 mouse-IgG2aFc (B7-H1-Ig) fusion protein nearly abolish T H17, but not T H1 and T H2, differentiation via direct interaction with the T cell. These effects were equally pronounced in the absence of programmed death-1 or B7.1 and B7.2 on the T cell side, thus providing clear evidence that B7-H1 modulates T cell differentiation via a novel receptor. Mechanistically, B7-H1 interfered with early TCR-mediated signaling and cytokine-mediated induction of the T H17-determining transcription factors retinoic acid-related orphan receptor g t and IFN regulator factor-4 in a programmed death-1 and B7-independent fashion. In an animal model of MS, active myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, B7-H1-Ig exhibited a significant and long-lasting effect on disease severity upon administration during the first 5 d of the priming phase, which was accompanied by reduced T H17 responses in the periphery and within the CNS. Importantly, B7-H1-Ig was even capable of interfering with T cell encephalitogenicity when interaction with the T cells occurred after priming using an adoptive transfer experimental autoimmune encephalomyelitis model. In line with this, both naive human CD4 + T cells and differentiated T H17 effector cells from MS patients were highly sensitive toward B7-H1-Ig-mediated T H17 suppression. Together, we propose the existence of a novel B7-H1-mediated immune-regulatory pathway in T cells, which selectively limits murine and human T H17 cell responses and might be therapeutically exploited to control T H17-mediated autoimmunity.
AB - It is currently acknowledged that T H17 cells are critically involved in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). In this article, we demonstrate that signals delivered by the coinhibitory molecule B7-homologue 1 (B7-H1) via a B7-homologue 1 mouse-IgG2aFc (B7-H1-Ig) fusion protein nearly abolish T H17, but not T H1 and T H2, differentiation via direct interaction with the T cell. These effects were equally pronounced in the absence of programmed death-1 or B7.1 and B7.2 on the T cell side, thus providing clear evidence that B7-H1 modulates T cell differentiation via a novel receptor. Mechanistically, B7-H1 interfered with early TCR-mediated signaling and cytokine-mediated induction of the T H17-determining transcription factors retinoic acid-related orphan receptor g t and IFN regulator factor-4 in a programmed death-1 and B7-independent fashion. In an animal model of MS, active myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, B7-H1-Ig exhibited a significant and long-lasting effect on disease severity upon administration during the first 5 d of the priming phase, which was accompanied by reduced T H17 responses in the periphery and within the CNS. Importantly, B7-H1-Ig was even capable of interfering with T cell encephalitogenicity when interaction with the T cells occurred after priming using an adoptive transfer experimental autoimmune encephalomyelitis model. In line with this, both naive human CD4 + T cells and differentiated T H17 effector cells from MS patients were highly sensitive toward B7-H1-Ig-mediated T H17 suppression. Together, we propose the existence of a novel B7-H1-mediated immune-regulatory pathway in T cells, which selectively limits murine and human T H17 cell responses and might be therapeutically exploited to control T H17-mediated autoimmunity.
KW - Chemistry
UR - http://www.scopus.com/inward/record.url?scp=84943545956&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1402746
DO - 10.4049/jimmunol.1402746
M3 - Journal articles
C2 - 26378076
VL - 195
SP - 3584
EP - 3595
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 8
ER -