TH Cells and Cytokines in Encephalitogenic Disorders

Abstract

The invasion of immune cells into the central nervous system (CNS) is a hallmark of the process we call neuroinflammation. Diseases such as encephalitides or multiple sclerosis (MS) are characterised by the dramatic influx of T lymphocytes and monocytes. The communication between inflammatory infiltrates and CNS resident cells is primarily mediated through cytokines. Over the years, numerous cytokine networks have been assessed to better understand the development of immunopathology in neuroinflammation. In MS for instance, many studies have shown that CD4+ T cells infiltrate the CNS and subsequently lead to immunopathology. Inflammatory CD4+ T cells, such as TH1, TH17, GM-CSF-producing helper T cells are big players in chronic neuroinflammation. Conversely, encephalitogenic or meningeal regulatory T cells (TREGs) and TH2 cells have been shown to drive a decrease in inflammatory functions in microglial cells and thus promote a neuroprotective microenvironment. Recent studies report overlapping as well as differential roles of these cells in tissue inflammation. Taken together, this suggests a more complex relationship between effector T cell subsets in neuroinflammation than has hitherto been established. In this overview, we review the interplay between helper T cell subsets infiltrating the CNS and how they actively contribute to neuroinflammation and degeneration. Importantly, in this context, we will especially focus on the current knowledge regarding the contribution of various helper cell subsets to neuroinflammation by referring to their helper T cell profile in the context of their target cell.

T cell phenotype switching in autoimmune disorders: Clinical significance of targeting metabolism

“…The pleiotropic cytokine IL‐6 inhibits the function of TGFβ (transforming growth factor β), thus disfavouring the Treg phenotype—which would suppress adaptive T cell responses—to promote the Th17 phenotype. The latter correlates with the incidence and severity of immune diseases, such as Rheumatoid Arthritis 7,8 and Multiple Sclerosis 9 (Figure 1). Similarly, increased Th1/Th17 with an enhanced glycolytic activity and decreased Treg populations are observed in patients affected by Psoriasis (autoimmune disease where T cells attack skin cells) 10 .…”

Neuroinflammation: Extinguishing a blaze of T cells

“…Several authors have pointed out the shortcomings of defining Th cells based on the cytokines they produce in the context of inflammation. [120][121][122] A more judicious alternative would be to classify them according to their effect on responder cells. 121,122 For example, a type 1 response refers to cellular immunity involving the secretion of IFNγ and GM-CSF and that targets myeloid cells including macrophages and microglia.…”

“…[120][121][122] A more judicious alternative would be to classify them according to their effect on responder cells. 121,122 For example, a type 1 response refers to cellular immunity involving the secretion of IFNγ and GM-CSF and that targets myeloid cells including macrophages and microglia. Type 2 responses affect polymorphnucleated cells like eosinophils, basophils, and mast cells through IL-4-, IL-5-, IL-9-, IL-13-, and IL-21-secreting Th cells.…”

“…Via the secretion of IL-17 and IL-23, type 3 Th cells target non-immune cells, especially at barrier sites, like BBB endothelium, astrocytes, and oligodendro cytes. 121,122 Yet, one cannot overlook the notion of plasticity when considering T cell functional classification (Figure 2). Indeed, the signaling dynamics of a given inflamed microenvironment have a profound impact on T cell subsets and their lineage fate.…”

“…Several authors have pointed out the shortcomings of defining Th cells based on the cytokines they produce in the context of inflammation 120‐122 . A more judicious alternative would be to classify them according to their effect on responder cells 121,122 .…”