Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity

Schnell, Alexandra; Huang, Lüping; Singer, Meromit; Singaraju, Anvita; Barilla, Rocky; Regan, Brianna M L; Bollhagen, Alina; Thakore, Pratiksha I.; Dionne, Danielle; Delorey, Toni; Pawlak, Mathias; Hörste, Gerd Meyer zu; Rozenblatt-Rosen, Orit; Irizarry, Rafael A.; Regev, Aviv; Kuchroo, Vijay K.

doi:10.1016/j.cell.2021.11.018

Cited by 136 publications

(125 citation statements)

References 95 publications

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“…In particular, transplanting stem cells into the gut of preclinical models of NDDs reduces the inflammatory microbiome not just in the gut but also in the brain accompanied by improvement in neurological functions. Whereas the present paper focuses on just four NDDs, other neurological disorders present with similar GBA alterations that accompany the disease progression, including Huntington's disease [139][140][141] and multiple sclerosis [142][143][144]. Accordingly, disease-specific tailoring of stem cell transplantation targeting GBA may provide disease-modifying outcomes for these neurological disorders.…”

Section: Discussionmentioning

confidence: 99%

Gut–Brain Axis as a Pathological and Therapeutic Target for Neurodegenerative Disorders

Toledo

Monroy

Salazar

et al. 2022

IJMS

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Human lifestyle and dietary behaviors contribute to disease onset and progression. Neurodegenerative diseases (NDDs), considered multifactorial disorders, have been associated with changes in the gut microbiome. NDDs display pathologies that alter brain functions with a tendency to worsen over time. NDDs are a worldwide health problem; in the US alone, 12 million Americans will suffer from NDDs by 2030. While etiology may vary, the gut microbiome serves as a key element underlying NDD development and prognosis. In particular, an inflammation-associated microbiome plagues NDDs. Conversely, sequestration of this inflammatory microbiome by a correction in the dysbiotic state of the gut may render therapeutic effects on NDDs. To this end, treatment with short-chain fatty acid-producing bacteria, the main metabolites responsible for maintaining gut homeostasis, ameliorates the inflammatory microbiome. This intimate pathological link between the gut and NDDs suggests that the gut-brain axis (GBA) acts as an underexplored area for developing therapies for NDDs. Traditionally, the classification of NDDs depends on their clinical presentation, mostly manifesting as extrapyramidal and pyramidal movement disorders, with neuropathological evaluation at autopsy as the gold standard for diagnosis. In this review, we highlight the evolving notion that GBA stands as an equally sensitive pathological marker of NDDs, particularly in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and chronic stroke. Additionally, GBA represents a potent therapeutic target for treating NDDs.

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Section: Discussionmentioning

confidence: 99%

Gut–Brain Axis as a Pathological and Therapeutic Target for Neurodegenerative Disorders

Toledo

Monroy

Salazar

et al. 2022

IJMS

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“…This finding is supported by another recent study by Hou et al ( 201 ), which also identifies CXCR6 to be a marker of GM-CSF- and IFNγ-expressing Th cells which may also secrete IL-17A, lending support to the potential of CXCR6 as a marker for the pathogenic Th17/exTh17 subsets. Furthermore, a recent study demonstrated that SLAMF6 + Th17 cells in secondary lymphoid organs and intestines represent a stem-like Th17 population that convert to CXCR6 + GM-CSF-secreting pathogenic Th cells that invade the CNS during EAE ( 202 ). The specific role of CXCR6 in recruiting Th17 cells into the CNS during EAE is not currently clear.…”

Section: Migratory Mechanisms Of Autoreactive Th Cells In Eae/msmentioning

confidence: 99%

Chemokine-Driven Migration of Pro-Inflammatory CD4+ T Cells in CNS Autoimmune Disease

et al. 2022

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Pro-inflammatory CD4+ T helper (Th) cells drive the pathogenesis of many autoimmune conditions. Recent advances have modified views of the phenotype of pro-inflammatory Th cells in autoimmunity, extending the breadth of known Th cell subsets that operate as drivers of these responses. Heterogeneity and plasticity within Th1 and Th17 cells, and the discovery of subsets of Th cells dedicated to production of other pro-inflammatory cytokines such as GM-CSF have led to these advances. Here, we review recent progress in this area and focus specifically upon evidence for chemokine receptors that drive recruitment of these various pro-inflammatory Th cell subsets to sites of autoimmune inflammation in the CNS. We discuss expression of specific chemokine receptors by subsets of pro-inflammatory Th cells and highlight which receptors may be tractable targets of therapeutic interventions to limit pathogenic Th cell recruitment in autoimmunity.

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“…With T cell activation comes clonal expansion, where an individual T cell will divide numerous times, and the TCR is heritably maintained during cell division [3]. In this way, sister clones can be tracked within or between tissues based on sharing of the TCR sequence [27][28][29]36,38,39,50,51]. Additionally, the TCR also acts as a set of features that influence T cell fate and function following antigen encounter [68,69,71].…”

Section: Trends Trends In In Immunology Immunologymentioning

confidence: 99%

TCR-sequencing in cancer and autoimmunity: barcodes and beyond

Pauken¹,

Lagattuta²,

Lu³

et al. 2022

Trends in Immunology

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Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity

Cited by 136 publications

References 95 publications

Gut–Brain Axis as a Pathological and Therapeutic Target for Neurodegenerative Disorders

Gut–Brain Axis as a Pathological and Therapeutic Target for Neurodegenerative Disorders

Chemokine-Driven Migration of Pro-Inflammatory CD4+ T Cells in CNS Autoimmune Disease

TCR-sequencing in cancer and autoimmunity: barcodes and beyond

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