{"id":111275,"date":"2020-08-13T17:02:35","date_gmt":"2020-08-14T00:02:35","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2020\/08\/intercellular-adhesion-molecule-1-icam-1-and-icam-2-differentially-contribute-to-peripheral-activation-and-cns-entry-of-autoaggressive-th1-and-th17-cells-in-experimental-autoimmune-encephalomyelitis"},"modified":"2020-08-13T17:02:35","modified_gmt":"2020-08-14T00:02:35","slug":"intercellular-adhesion-molecule-1-icam-1-and-icam-2-differentially-contribute-to-peripheral-activation-and-cns-entry-of-autoaggressive-th1-and-th17-cells-in-experimental-autoimmune-encephalomyelitis","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2020\/08\/intercellular-adhesion-molecule-1-icam-1-and-icam-2-differentially-contribute-to-peripheral-activation-and-cns-entry-of-autoaggressive-th1-and-th17-cells-in-experimental-autoimmune-encephalomyelitis","title":{"rendered":"Intercellular Adhesion Molecule-1 (ICAM-1) and ICAM-2 Differentially Contribute to Peripheral Activation and CNS Entry of Autoaggressive Th1 and Th17 Cells in Experimental Autoimmune Encephalomyelitis"},"content":{"rendered":"

<\/a><\/p>\n

Scientists from 4 different Swiss universities describe how adhesion molecules activate autoaggressive immune cells and drive their infiltration in the nervous system in a model of multiple sclerosis.<\/p>\n

Click to read the paper published in Frontiers in Immunology: https:\/\/fro.ntiers.in\/tp1U<\/a><\/p>\n

\n

In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), myelin-specific T cells are activated in the periphery and differentiate in T helper (Th) 1 and Th17 effector cells, which cross the blood-brain barrier (BBB) to reach the central nervous system (CNS), where they induce neuroinflammation. Here, we explored the role of intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 in the activation of na\u00efve myelin-specific T cells and in the subsequent migration of differentiated encephalitogenic Th1 and Th17 cells across the BBB in vitro<\/i> and in vivo<\/i>. While on antigen-presenting cells ICAM-1, but not ICAM-2 was required for the activation of na\u00efve CD4+<\/sup> T cells, endothelial ICAM-1 and ICAM-2 mediated both Th1 and Th17 cell migration across the BBB. ICAM-1\/-2-deficient mice developed ameliorated typical and atypical EAE transferred by encephalitogenic Th1 and Th17 cells, respectively. Our study underscores important yet cell-specific contributions for ICAM-1 and ICAM-2 in EAE pathogenesis.<\/p>\n

Multiple sclerosis (MS) is considered an autoimmune inflammatory demyelinating disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE), a prototypic animal model for MS, mimics many aspects of the acute inflammatory phase of the human disease (1<\/a>). In EAE, na\u00efve myelin-reactive CD4+<\/sup> T cells are activated and differentiated in peripheral lymphoid tissue into encephalitogenic Th1 or Th17 cells, which travel in the blood circulation to the CNS. After crossing the blood-brain barrier (BBB) they next infiltrate in the CNS parenchyma, leading to clinical manifestation of the disease (2<\/a>). EAE can be actively induced by immunization with CNS myelin antigens emulsified in complete Freund\u2019s adjuvant (aEAE) or by injection of myelin-reactive CD4+<\/sup> T cells into syngeneic na\u00efve recipients (tEAE) (3<\/a>, 4<\/a>).<\/p>\n

Activation of na\u00efve CD4+<\/sup> T cells during aEAE occurs in the draining peripheral lymph nodes (dLNs), where T cells recognize their cognate antigen (Ag) on antigen-presenting cells (APCs) forming periodic contacts between the T-cell receptor (TCR) and the myelin oligodendrocyte glycoprotein (MOG)aa35\u221255<\/sub> peptide loaded major histocompatibility complex (pMHC) on the APCs, referred to as the immunological synapse (IS) (5, 6). The fate of na\u00efve T cells is determined within hours after Ag exposure by interacting with APCs in LN. The interaction between the integrin lymphocyte function associated antigen-1 (LFA-1) on the T cells and its ligand intercellular adhesion molecule-1 (ICAM-1) on the APCs is suggested to be involved in modulating the IS. However, APCs additionally express ICAM-2, an alternate ligand of LFA-1.<\/p>\n","protected":false},"excerpt":{"rendered":"

Scientists from 4 different Swiss universities describe how adhesion molecules activate autoaggressive immune cells and drive their infiltration in the nervous system in a model of multiple sclerosis. Click to read the paper published in Frontiers in Immunology: https:\/\/fro.ntiers.in\/tp1U In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), myelin-specific T cells are [\u2026]<\/p>\n","protected":false},"author":534,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,47],"tags":[],"class_list":["post-111275","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-neuroscience"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/111275","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/534"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=111275"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/111275\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=111275"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=111275"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=111275"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}