Oligodendrocytes regulate the adhesion molecule ICAM‐1 in neuroinflammation

Abstract

Recently, oligodendrocytes (Ol) have been attributed potential immunomodulatory effects. Yet, the exact mode of interaction with pathogenic CNS infiltrating lymphocytes remains unclear. Here, we attempt to dissect mechanisms of Ol modulation during neuroinflammation and characterize the interaction of Ol with pathogenic T cells. RNA expression analysis revealed an upregulation of immune-modulatory genes and adhesion molecules (AMs), ICAM-1 and VCAM-1, in Ol when isolated from mice undergoing experimental autoimmune encephalomyelitis (EAE). To explore whether AMs are involved in the interaction of Ol with infiltrating T cells, we performed co-culture studies on mature Ol and Th1 cells. Live cell imaging analysis showed direct interaction between both cell types. Eighty percentage of Th1 cells created contacts with Ol that lasted longer than 15 min, which may be regarded as physiologically relevant. Exposure of Ol to Th1 cells or their supernatant resulted in a significant extension of Ol processes, and upregulation of AMs as well as other immunomodulatory genes. Our observations indicate that blocking of oligodendroglial ICAM-1 can reduce the number of Th1 cells initially contacting the Ol. These results suggest that AMs may play a role in the interaction between Ol and Th1 cells. We identified Ol interacting with CD4 + cells in vivo in spinal cord tissue of EAE diseased mice indicating that our in vitro findings are of interest to further scientific research in this field. Further characterization and understanding of Ol interaction with infiltrating cells may lead to new therapeutic strategies enhancing Ol protection and remyelination potential. Oligodendrocytes regulate immune modulatory genes and adhesion molecules during autoimmune neuroinflammation Oligodendrocytes interact with Th1 cells in vitro in a physiologically relevant manner Adhesion molecules may be involved in Ol-Th1 cell interaction.

Immune–stem cell crosstalk in the central nervous system: how oligodendrocyte progenitor cells interact with immune cells

“…This upregulation has also been described in vitro , when OPCs are exposed to an inflammatory environment, such as the secretome of Th1 cells. This increased intercellular adhesion molecule‐1 and vascular cell adhesion molecule 1 expression in OPCs augments the formation of stable contacts between Th1 cells and OPCs, increasing OPC–T‐cell interactions 57 …”

“…On the one hand, activated Th1 cell supernatant impairs human A2B5 + OPC differentiation into O4‐ and GalC‐expressing oligodendrocytes 55 . On the other hand, murine Th1 cell supernatants and OPC–Th1 cell cocultures alter OPC morphology, leading to a significant extension of processes, which suggests increased differentiation 56,57 . IFNγ, a key cytokine secreted by CD4 + Th1 cells, does not explain these contradictory results, as exposure of OPCs to T‐cell–derived IFNγ enhances OPC proliferation while inhibiting OPC differentiation and increasing oligodendrocyte apoptosis 58 .…”

“…55 On the other hand, murine Th1 cell supernatants and OPC-Th1 cell cocultures alter OPC morphology, leading to a significant extension of processes, which suggests increased differentiation. 56,57 IFNc, a key cytokine secreted by CD4 + Th1 cells, does not explain these contradictory results, as exposure of OPCs to T-cell-derived IFNc enhances OPC proliferation while inhibiting OPC differentiation and increasing oligodendrocyte apoptosis. 58 Therefore, the effect of Th1 cells on OPC biology remains to be elucidated.…”

“…This increased intercellular adhesion molecule-1 and vascular cell adhesion molecule 1 expression in OPCs augments the formation of stable contacts between Th1 cells and OPCs, increasing OPC-T-cell interactions. 57 In summary, OPCs can bidirectionally modulate Tcell-mediated inflammation depending on the CNS environment, through either cell-cell contact via the expression of antigen-presenting molecules, adhesion molecules and other receptors, or through the secretion of cytokines and chemokines (Figure 1).…”

Beyond Myelination: Possible Roles of the Immune Proteasome in Oligodendroglial Homeostasis and Dysfunction

“…Over the following thirty years (1992-2022), sixteen more articles were published concerning the matter. Of these, eight investigated the expression of MHC I ( Horwitz et al, 1999 ; Baerwald et al, 2000 ; Redwine et al, 2001 ; Hoftberger et al, 2004 ; Na et al, 2008 ; Pan et al, 2020 ; González-Alvarado et al, 2022 ) and eight investigated the expression of MHC II on OLNs ( Bergsteindottir et al, 1992 ; Horwitz et al, 1999 ; Yin et al, 2008 ; Itoh et al, 2009 ; Falcão et al, 2018 ; Jäkel et al, 2019 ; Nagy et al, 2020 ; Pan et al, 2020 ). The mechanistic and functional aspects reported in these publications will be further discussed in section 4 of the review.…”