{"id":407415,"date":"2026-03-27T21:20:08","date_gmt":"2026-03-27T21:20:08","guid":{"rendered":"https:\/\/www.europesays.com\/ie\/407415\/"},"modified":"2026-03-27T21:20:08","modified_gmt":"2026-03-27T21:20:08","slug":"gut-immune-link-identified-in-multiple-sclerosis-related-neuroinflammation","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/ie\/407415\/","title":{"rendered":"Gut-Immune Link Identified in Multiple Sclerosis-Related Neuroinflammation"},"content":{"rendered":"

\"Nerve<\/a>Credit: Juan Gaertner\/Science Photo Library\/Getty Images<\/p>\n

Multiple sclerosis (MS) is a debilitating neurological disorder caused by malfunctioning immune responses that target the brain and spinal cord of the central nervous system (CNS). New research led by Shohei Suzuki, MD, PhD, assistant professor, division of gastroenterology and hepatology, and Tomohisa Sujino, PhD, associate professor, School of Medicine, at Keio University, Japan, has now indicated how the gut can initiate neuroinflammation in multiple sclerosis.<\/p>\n

Their study found that intestinal epithelial cells (IECs) promote the development of pathogenic T cells that migrated to the spinal cord and induced disease symptoms in mouse models of the disorder.<\/p>\n

The researchers examined intestinal tissues from patients with MS and mice with experimental autoimmune encephalomyelitis (EAE), a close analog of MS. In both cases, they observed an increase in TH17 cells and an upregulation of major histocompatibility complex class II (MHC II) expression in IECs. Deleting MHC II in IECs reduced the accumulation of TH17 cells in the gut and lowered the severity of EAE. They suggest the results could inform future strategies for developing targeted therapeutics against autoimmunity.<\/p>\n

\u201cWhile current therapies for MS often target B cells, our study highlights the gut as an important therapeutic site,\u201d Suzuki commented. \u201cModulating intestinal microbiota or antigen-presenting activity of IECs represents new approaches to treating autoimmune neurological diseases.\u201d<\/p>\n

Suzuki, Sujino, and colleagues reported on their findings in Science Immunology, in a paper titled \u201cIntestinal Epithelial MHC Class II Induces Encephalitogenic CD4\u207a T Cells and Initiates Central Nerves System Autoimmunity<\/a>,\u201d in which they concluded, \u201cOur findings reveal an interaction between gut IECs and neuroinflammatory diseases through MHC II expression in human MS and mouse EAE, providing a mechanistic link between gut immune education and CNS autoimmunity and opening new avenues for targeting intestinal immunity in neuroinflammatory diseases.<\/p>\n

Failure of the immune system to distinguish \u2018self\u2019 from \u2018non-self\u2019 entities leads to excessive autoimmune responses against self-proteins like myelin, which forms a protective covering on the neurons. Multiple factors influence the onset and progression of MS, including genetic susceptibility, environmental triggers, and, more recently, the gut microenvironment. Patients with MS exhibit alterations in their gut microbiota, while the gut microbiota and microbial metabolites play a pivotal role in shaping the chronic autoreactive immune responses.\u00a0 \u201c\u2026\u00a0 in an experimental autoimmune encephalomyelitis (EAE) model, commensal or specific microbes were found to be essential for disease initiation and progression,\u201d the authors wrote.<\/p>\n

However, in trying to define this gut\u2013CNS axis, the cellular mechanisms that relay the gut-derived signals to the immune system to influence autoimmune inflammation in the CNS remain poorly understood. \u201cIncreasing evidence shows that the gut microbiota influences neurological diseases such as Parkinson\u2019s, Alzheimer\u2019s, and MS,\u201d Sujino stated. \u201cHowever, the mechanisms linking gut microbes, intestinal immunity, and brain inflammation remain unclear. We were keen to identify how gut immune responses contribute to neuroinflammatory diseases.\u201d<\/p>\n

Prior research has shown that gut-derived signals can promote the differentiation of T cells into pathogenic T helper 17 (TH17) in mouse models of MS. Recent studies have suggested that IECs can function as antigen presenting cells that help induce these pathogenic cells, but the underlying mechanisms have been unclear.<\/p>\n

Building on their previous observation that mild intestinal (ileal) inflammation exists in experimental autoimmune encephalomyelitis (EAE), which is a mouse model of MS, the authors set out to test whether similar inflammation is present in patients with MS. By performing single-cell RNA sequencing on intestinal biopsies, the team identified that inflammatory Th17 cells accumulate in the mouse EAE model as well as in the intestine of patients with MS, suggesting a conserved gut\u2013CNS axis that may be active in human diseases.<\/p>\n

In both EAE mice and patients with MS, intestinal epithelial cells upregulated antigen presentation pathways. Particularly, epithelial cells in the ileum had higher expression of major histocompatibility complex class II (MHC II) that presents antigens to CD4+\u00a0T cells. \u201cClinically, patients with MS exhibited an increased expression of epithelial MHC II\u2013associated genes and an accumulation of CD4 T cells in the small intestine, suggesting the conservation of this gut-CNS axis in human diseases,\u201d the scientists stated. Experiments showed that selective deletion of MHC II in IECs reduced pathogenic Th17 cell generation and disease severity. \u201cConditional deletion of MHC II in IECs showed that epithelial antigen presentation was indispensable for the local expansion of pathogenic Th17 cells in the gut and their subsequent migration to the CNS,\u201d the team stated.<\/p>\n

\"ImmunofluorescenceImmunofluorescence analysis was performed on terminal ileum samples from Cnt, IEC\u0394MHCII, Cnt + EAE, and IEC\u0394MHCII + EAE mice. A total of 3\u20135 tissue sections were analyzed per
mouse, with three mice included in each group. [Shohei Suzuki]IECs do not typically present antigens to immune cells. So, the team conducted co-culture assays to test the antigen presentation function of IECs. Their findings demonstrate that IECs can directly present antigens in an MHC II-dependent manner to prime CD4+\u00a0T cells in the gut. Notably, in these assays, IECs induced Th17 polarization of activated CD4+\u00a0T cells. It became clear that the gut was a critical site for immune activation of pathogenic CD4+\u00a0T cells that polarized into pro-inflammatory Th17 cells. \u201cThese findings provide direct functional evidence that IEC-expressed MHC II is sufficient to drive Th17 polarization from primed CD4 T cells in an antigen-dependent manner, supporting a direct role for IECs as non-professional antigen-presenting cells,\u201d the scientists reported.<\/p>\n

To investigate whether the Th17 cells directly contribute to the pool of autoreactive cells in the CNS, they used transgenic mice that express the\u00a0Kaede\u00a0protein, which undergoes photoconversion from green to red fluorescence upon exposure to violet light. This model allowed for precise tracking of pathogenic Th17 cells induced in the intestinal lamina propria that then migrate to the spinal cord and drive neuroinflammation.<\/p>\n

Taken together, the study findings reveal a critical role for MHC II expressed by IECs in the expansion of pathogenic Th17 cells that subsequently migrate to the CNS during EAE, providing a mechanistic link between gut immune responses and autoimmune neuroinflammatory diseases. The results demonstrate that while systemic circulation allows T cell exchange across immune tissues, the epithelial\u2013immune interactions within the gut mucosal compartment can essentially shape effector T cell responses in the brain.<\/p>\n

\u201cThis study reveals a previously unknown role of IECs in antigen presentation and Th17 programming, thereby defining a gut-CNS immunological axis with important implications for understanding and treating autoimmune neuroinflammation,\u201d the authors concluded. \u201cOur findings suggest that the modulation of epithelial antigen presentation could serve as a novel therapeutic approach for MS and related diseases. Given the accessibility of the gut epithelium to dietary, microbial, and pharmacological interventions, targeting IEC\u2013T cell interactions may offer a tractable strategy for immunomodulation.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"Credit: Juan Gaertner\/Science Photo Library\/Getty Images Multiple sclerosis (MS) is a debilitating neurological disorder caused by malfunctioning immune…\n","protected":false},"author":2,"featured_media":407416,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":"","_share_on_mastodon":"0"},"categories":[78],"tags":[18,135,19,17,5,5632,39996],"class_list":["post-407415","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-eire","tag-health","tag-ie","tag-ireland","tag-news","tag-topics","tag-translational-medicine"],"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@ie\/116303234997948902","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/407415","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/comments?post=407415"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/407415\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media\/407416"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media?parent=407415"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/categories?post=407415"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/tags?post=407415"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}