New Insights into the Role of IL-1β in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis

Abstract

Multiple sclerosis, and its animal model experimental autoimmune encephalomyelitis, are neuroinflammatory diseases driven by autoreactive pathogenic TH cells which elicit demyelination and axonal damage. How TH cells acquire pathogenicity and communicate with myeloid cells and cells of the central nervous system remain unclear. IL-1β is recognized to play an important role in EAE and perhaps MS. Clinical EAE is significantly attenuated in IL-1 receptor-deficient and IL-1β-deficient mice, and IL-1β is found in the blood, cerebrospinal fluid, and CNS lesions of MS patients. Here, we will focus on new reports which elucidate the cellular sources of IL-1β and its actions during EAE, in both lymphoid tissues and within the CNS. Several immune cell types serve as critical producers of IL-1β during EAE, with the cytokine inducing responses in hematopoietic and non-hematopoietic cells. These findings from the EAE model should inspire efforts towards investigating the therapeutic potential of IL-1 blockade in MS.

Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4+ T cells to cytokines

“…Future scRNA-seq studies of inflamed tissues will provide an opportunity to investigate these effects in greater detail directly. Understanding this will be key in the development of drug targets for autoimmune disease, as Th17cytokines are known to promote inflammation in multiple sclerosis [49][50][51] .…”

Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4+ T cells to cytokines

“…Understanding this will be key in the development of drug targets for autoimmune disease, as IL-17 and other Th17-cytokines are known to promote inflammation, for example in MS patients and animal models of disease [49][50][51] .…”

Environmental Control of Astrocyte Pathogenic Activities in CNS Inflammation

“…We first analyzed the UPR in astrocytes activated with IL-1b and TNF-a, pro-inflammatory cytokines considered important contributors to multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) pathogenesis (Lin and Edelson, 2017;Valentin-Torres et al, 2016). Astrocyte treatment with IL-1b and TNF-a activated the transcription factor nuclear factor kB (NF-kB) ( Figure 2B), associated with astrocyte pro-inflammatory and neurotoxic activities (Liddelow and Barres, 2017).…”