T cell derived HB-EGF prevents Th17 cell differentiation in an autocrine way

Macdonald, Felicity; J, van Loosdregt; Zaiss, Dietmar M.

doi:10.1101/2021.02.09.430418

Cited by 3 publications

(2 citation statements)

References 35 publications

(65 reference statements)

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“…Genes related to tissue homing and residency, including KLRB1 and the chemokine receptor CXCR6 ( 20 – 22 ), were solely upregulated in cluster 0. This cluster showed further transcript enrichments for proinflammatory mediators including IL-22, as well as for heparin-binding EGF (HBEGF), a marker suggested to shape antigen-specific CD4 + T cell responses and constrain Th17 differentiation ( 23 ). Upregulated genes involved in various metabolic pathways were observed in cluster 1, including FABP5 and ODC1 , both involved in lipid metabolism of tissue-resident lymphocytes ( 24 , 25 ).…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 mRNA vaccination–induced immunological memory in human nonlymphoid and lymphoid tissues

Proß,

Sattler,

Lukassen

et al. 2023

Journal of Clinical Investigation

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Tissue-resident lymphocytes provide organ-adapted protection against invading pathogens. Whereas their biology has been examined in great detail in various infection models, their generation and functionality in response to vaccination have not been comprehensively analyzed in humans. We therefore studied SARS-CoV-2 mRNA vaccine–specific T cells in surgery specimens of kidney, liver, lung, bone marrow, and spleen compared with paired blood samples from largely virus-naive individuals. As opposed to lymphoid tissues, nonlymphoid organs harbored significantly elevated frequencies of spike-specific CD4 + T cells compared with blood showing hallmarks of tissue residency and an expanded memory pool. Organ-derived CD4 + T cells further exhibited increased polyfunctionality over those detected in blood. Single-cell RNA-Seq together with T cell receptor repertoire analysis indicated that the clonotype rather than organ origin is a major determinant of transcriptomic state in vaccine-specific CD4 + T cells. In summary, our data demonstrate that SARS-CoV-2 vaccination entails acquisition of tissue memory and residency features in organs distant from the inoculation site, thereby contributing to our understanding of how local tissue protection might be accomplished.

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Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 mRNA vaccination–induced immunological memory in human nonlymphoid and lymphoid tissues

Proß,

Sattler,

Lukassen

et al. 2023

Journal of Clinical Investigation

View full text Add to dashboard Cite

show abstract

“…Tissue homing and residency related genes including KLRB1 (encoding CD161) and the chemokine receptor CXCR6 ( 22-24 ) were solely upregulated in cluster 0. This cluster showed further transcript enrichments for proinflammatory mediators including IL-22, as well as for heparin-binding EGF (HBEGF), a marker suggested to shape antigen-specific CD4 + T cell responses and constraining Th17 differentiation ( 25 ). In contrast, upregulated genes involved in various metabolic pathways were observed for cluster 1.…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV2 mRNA-vaccination-induced Immunological Memory in Human Non-Lymphoid and Lymphoid Tissues

Proß

Sattler

Lukassen

et al. 2023

Preprint

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Tissue-resident lymphocytes provide organ-adapted protection against invading pathogens. Whereas their biology has been examined in great detail in various infection models, their generation and functionality in response to vaccination has not been comprehensively analyzed in humans. We therefore studied SARS-CoV2 mRNA-vaccine-specific T cells in surgery specimens of kidney, liver, lung, bone marrow and spleen in comparison to paired blood samples from largely virus-naive individuals. As opposed to lymphoid tissues, non-lymphoid organs harbored significantly elevated frequencies of Spike-specific CD4+ T cells compared to paired peripheral blood showing hallmarks of tissue residency and an expanded memory pool. Organ-derived, vaccine-specific T helper (Th) cells were characterized by increased portions of multifunctional cells over those detected in blood. Single-cell RNA sequencing revealed functional rather than organ-specific clusters of Spike-reactive Th cells, indicating similar diversification programs across tissues. T cell receptor (TCR) repertoire analysis indicated that the TCR sequence is a major determinant of transcriptomic state in tissue-resident, vaccine-specific CD4+ T cells. In summary, our data demonstrate that SARS-CoV2 vaccination entails acquisition of tissue memory and residency features in organs distant from the inoculation site, thereby contributing to our understanding of how local tissue protection might be accomplished.

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The neuroimmune axis of Alzheimer’s disease

2023

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Alzheimer’s disease (AD) is a genetically complex and heterogeneous disorder with multifaceted neuropathological features, including β-amyloid plaques, neurofibrillary tangles, and neuroinflammation. Over the past decade, emerging evidence has implicated both beneficial and pathological roles for innate immune genes and immune cells, including peripheral immune cells such as T cells, which can infiltrate the brain and either ameliorate or exacerbate AD neuropathogenesis. These findings support a neuroimmune axis of AD, in which the interplay of adaptive and innate immune systems inside and outside the brain critically impacts the etiology and pathogenesis of AD. In this review, we discuss the complexities of AD neuropathology at the levels of genetics and cellular physiology, highlighting immune signaling pathways and genes associated with AD risk and interactions among both innate and adaptive immune cells in the AD brain. We emphasize the role of peripheral immune cells in AD and the mechanisms by which immune cells, such as T cells and monocytes, influence AD neuropathology, including microglial clearance of amyloid-β peptide, the key component of β-amyloid plaque cores, pro-inflammatory and cytotoxic activity of microglia, astrogliosis, and their interactions with the brain vasculature. Finally, we review the challenges and outlook for establishing immune-based therapies for treating and preventing AD.

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T cell derived HB-EGF prevents Th17 cell differentiation in an autocrine way

Cited by 3 publications

References 35 publications

SARS-CoV-2 mRNA vaccination–induced immunological memory in human nonlymphoid and lymphoid tissues

SARS-CoV-2 mRNA vaccination–induced immunological memory in human nonlymphoid and lymphoid tissues

SARS-CoV2 mRNA-vaccination-induced Immunological Memory in Human Non-Lymphoid and Lymphoid Tissues

The neuroimmune axis of Alzheimer’s disease

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