CD70 defines a subset of proinflammatory and CNS-pathogenic TH1/TH17 lymphocytes and is overexpressed in multiple sclerosis

Abstract

CD70 is the unique ligand of CD27 and is expressed on immune cells only upon activation. Therefore, engagement of the costimulatory CD27/CD70 pathway is solely dependent on upregulation of CD70. However, the T cell-intrinsic effect and function of human CD70 remain underexplored. Herein, we describe that CD70 expression distinguishes proinflammatory CD4 + T lymphocytes that display an increased potential to migrate into the central nervous system (CNS). Upregulation of CD70 on CD4 + T lymphocytes is induced by TGF-β1 and TGF-β3, which promote a pathogenic phenotype. In addition, CD70 is associated with a T H 1 and T H 17 profile of lymphocytes and is important for T-bet and IFN-γ expression by both T helper subtypes. Moreover, adoptive transfer of CD70 −/− CD4 + T lymphocytes induced less severe experimental autoimmune encephalomyelitis (EAE) disease than transfer of WT CD4 + T lymphocytes. CD70 + CD4 + T lymphocytes are found in the CNS during acute autoimmune inflammation in humans and mice, highlighting CD70 as both an immune marker and an important costimulator of highly pathogenic proinflammatory T H 1/T H 17 lymphocytes infiltrating the CNS.

CCL3 contributes to secondary damage after spinal cord injury

“…We cannot exclude that the Q-PCR on the whole injured spinal cord tissue is not sensitive enough to detect CCR4 expression levels on the individual cell level. [46] Bmp7 (Bone morphogenetic protein 7) − 3.24 0.036 Anti-inflammatory protein, neuroprotective function [47,48] CCl4 (CCL4) − 5.27 0.009 CCR1 agonist, role in wound repair and inflammation [49] Ccl11 (CCL11, eotaxin-1) − 5.98 0.021 Eosinophil chemotactic protein [50] CCl12 (CCL12) − 4.39 0.035 Pro-inflammatory cytokine [51] Cd70 (CD70) − 3.52 0.009 Pro-inflammatory, promoting T cell responses [52] Cx3cl1 (CX3CL1, Fractalkine) − 5.36 0.003 Chemotactic cytokine [53] Ifna2 (IFNα2) − 5.3 0.003 Pro-inflammatory cytokine with role in anti-tumor immunity [54] Il12b (IL12p40) − 4.90 0.008 Pro-inflammatory cytokine [55] Il16 (IL16) − 9.67 0.049 Chemoattractant for lymphocytes and macrophages [56] Il17f (IL17F) − 5.24 0.001 Pro-inflammatory cytokine [57] Il1a Gene expression changes were assessed using RT2 profiler cytokine array (PAMM-150Z), n = 3 mice/group and time point…”

RNA-binding protein altered expression and mislocalization in MS

“…The autopsies on patients with MS 8 from the Centre de Recherche du Centre Hospitalier de l'Université de Montréal had informed consent and were in accordance with institutional guidelines and approval by the local Centre Hospitalier de l'Université de Montréal ethics committee (HD04.046 and BH07.001). 9 The use of tissue from the Montreal Neurological Institute, McGill University, was approved by the McGill University Health Center Research Ethics Board. The human samples that were used are described in the e-methods (links.lww.com/NXI/A221).…”

A Two-Step Process of Effector Programming Governs CD4+ T Cell Fate Determination Induced by Antigenic Activation in the Steady State

“…Th1 and Th17 effector cells (Dhaeze et al, 2019) Cdk1 regulates Cdk2/cyclin A2 activity (Diril et al, 2012) Cdr2 correlates with attenuated hypoxia-inducible factor responses (Balamurugan et al, 2009) Cxcr3 required for optimal differentiation of IFN-gsecreting Th1 effector cells (Groom et al, 2012) Cxcr5 mediates co-localization of effector Tfh cells and B cells in lymphoid organs during arthritis pathogenesis (Moschovakis et al, 2017) Dusp14 regulates T cell proliferation and cytokine production (Yang et al, 2014) Eea1 regulates the polarization of T cell and NK cell cytotoxic granules (Chiang et al, 2017) Egr4 interaction with nuclear mediator NF-kB regulates the transcription of inflammatory cytokines (Wieland et al, 2005) Fgf2 synergistically exacerbates tissue inflammation by regulating the production of cytokines and chemokines (Shao et al, 2017) Foxm1 increases Ube2c transcription in glioma cells (Guo et al, 2017) Il12rb2 modulates the differentiation of IFN-g + Th1 effector cells (Bettelli and Kuchroo, 2005;Martínez-Barricarte et al, 2018) Il13 mediates the expansion of Th2 cells (Deepak and Acharya, 2012;Scalzo-Inguanti and Plebanski, 2011) Il1r2 negatively regulates IL-1 signaling (Peters et al, 2013) Il9r mediates Th17-driven inflammatory disease (Li et al, 2010;Nowak et al, 2009) Kif4 suppresses the activity of DNA repair enzyme poly(ADP-ribose) polymerase-1 (Midorikawa et al, 2006) Table 1. Continued…”