» Articles » PMID: 26378076

B7-H1 Selectively Controls TH17 Differentiation and Central Nervous System Autoimmunity Via a Novel Non-PD-1-Mediated Pathway

Overview
Journal J Immunol
Date 2015 Sep 18
PMID 26378076
Citations 9
Authors
Affiliations
Soon will be listed here.
Abstract

It is currently acknowledged that TH17 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 TH17, but not TH1 and TH2, 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 TH17-determining transcription factors retinoic acid-related orphan receptor γ 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 TH17 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 TH17 effector cells from MS patients were highly sensitive toward B7-H1-Ig-mediated TH17 suppression. Together, we propose the existence of a novel B7-H1-mediated immune-regulatory pathway in T cells, which selectively limits murine and human TH17 cell responses and might be therapeutically exploited to control TH17-mediated autoimmunity.

Citing Articles

PD-L1: From cancer immunotherapy to therapeutic implications in multiple disorders.

Lee D, Cho M, Kim E, Seo Y, Cha J Mol Ther. 2024; 32(12):4235-4255.

PMID: 39342430 PMC: 11638837. DOI: 10.1016/j.ymthe.2024.09.026.


Advances in immune checkpoint-based immunotherapies for multiple sclerosis: rationale and practice.

Daei Sorkhabi A, Komijani E, Sarkesh A, Shadbad P, Aghebati-Maleki A, Aghebati-Maleki L Cell Commun Signal. 2023; 21(1):321.

PMID: 37946301 PMC: 10634124. DOI: 10.1186/s12964-023-01289-9.


Impact of disease-modifying therapy on dendritic cells and exploring their immunotherapeutic potential in multiple sclerosis.

Liu C, Zhu J, Mi Y, Jin T J Neuroinflammation. 2022; 19(1):298.

PMID: 36510261 PMC: 9743681. DOI: 10.1186/s12974-022-02663-z.


Plasma protein profiling reveals dynamic immunomodulatory changes in multiple sclerosis patients during pregnancy.

Papapavlou Lingehed G, Hellberg S, Huang J, Khademi M, Kockum I, Carlsson H Front Immunol. 2022; 13:930947.

PMID: 35967338 PMC: 9373039. DOI: 10.3389/fimmu.2022.930947.


PD-1/PD-L1 Axis as a Potential Therapeutic Target for Multiple Sclerosis: A T Cell Perspective.

Li H, Zheng C, Han J, Zhu J, Liu S, Jin T Front Cell Neurosci. 2021; 15:716747.

PMID: 34381337 PMC: 8350166. DOI: 10.3389/fncel.2021.716747.