Aging‐related cell type‐specific pathophysiologic immune responses that exacerbate disease severity in aged COVID‐19 patients

Airborne pathogens and environmental stimuli evoke immune responses in the lung. It is critical to health that these responses be controlled to prevent tissue damage and the compromise of organ function. Resolution of inflammation is a dynamic process that is coordinated by biochemical and cellular mechanisms. Recently, specialized proresolving mediators (SPMs) have been identified in resolution exudates. These molecules orchestrate anti-inflammatory and proresolving actions that are cell type specific. In this review, we highlight SPM biosynthesis, the influence of SPMs on the innate and adaptive immune responses in the lung, as well as recent insights from SPMs on inflammatory disease pathophysiology. Uncovering these mediators and cellular mechanisms for resolution is providing new windows into physiology and disease pathogenesis.

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Toll-like receptor-induced innate immune responses in non-parenchymal liver cells are cell type-specific

Immunology ◽

10.1111/j.1365-2567.2009.03179.x ◽

2010 ◽

Vol 129 (3) ◽

pp. 363-374 ◽

Cited By ~ 116

Author(s):

Jun Wu ◽

Zhongji Meng ◽

Min Jiang ◽

Ejuan Zhang ◽

Martin Trippler ◽

...

Keyword(s):

Immune Responses ◽

Liver Cells ◽

Innate Immune ◽

Innate Immune Responses ◽

Toll Like Receptor ◽

Cell Type ◽

Parenchymal Liver ◽

Cell Type Specific

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W1707 TLR Induced Innate Immune Responses in Non-Parenchymal Liver Cells Are Cell Type-Specific

Gastroenterology ◽

10.1016/s0016-5085(08)63906-2 ◽

2008 ◽

Vol 134 (4) ◽

pp. A-835-A-836

Author(s):

Jun Wu ◽

Mengji Lu ◽

Joerg F. Schlaak

Keyword(s):

Immune Responses ◽

Liver Cells ◽

Innate Immune ◽

Innate Immune Responses ◽

Cell Type ◽

Parenchymal Liver ◽

Cell Type Specific

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MAFB surrogates the glucocorticoid receptor ability to induce tolerogenesis in dendritic cells

10.1101/2021.07.27.453975 ◽

2021 ◽

Author(s):

Octavio Morante-Palacios ◽

Laura Ciudad ◽

Raphael Micheroli ◽

Carlos de la Calle-Fabregat ◽

Tianlu Li ◽

...

Keyword(s):

Dendritic Cells ◽

Immune Responses ◽

Glucocorticoid Receptor ◽

Inflammatory Diseases ◽

Dna Demethylation ◽

Regulatory Mechanisms ◽

Cell Type ◽

Cell Type Specific

Glucocorticoids (GCs) exert potent anti-inflammatory effects in immune cells through the glucocorticoid receptor (GR). Dendritic cells (DCs), central actors for coordinating immune responses, acquire tolerogenic properties in response to GCs. Tolerogenic DCs (tolDCs) have emerged as a potential treatment for various inflammatory diseases. To date, the underlying cell type-specific regulatory mechanisms orchestrating GC-mediated acquisition of immunosuppressive properties remain poorly understood. In this study, we investigated the transcriptomic and epigenomic remodeling associated with differentiation to DCs in the presence of GCs. Our analysis demonstrates a major role of MAFB in this process, in synergy with GR. GR and MAFB both interact with methylcytosine dioxygenase TET2 and bind to genomic loci that undergo specific demethylation in tolDCs. We also show that the role of MAFB is more extensive, binding to thousands of genomic loci in tolDCs. Finally, MAFB knockdown erases the tolerogenic properties of tolDCs and reverts the specific DNA demethylation and gene upregulation. The preeminent role of MAFB is also demonstrated in vivo for myeloid cells from synovium in rheumatoid arthritis following GC treatment. Our results imply that, once directly activated by GR, MAFB takes over the main roles to orchestrate the epigenomic and transcriptomic remodeling that define the tolerogenic phenotype.

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Macrophage-specific MHCII expression is regulated by a remote Ciita enhancer controlled by NFAT5

Journal of Experimental Medicine ◽

10.1084/jem.20180314 ◽

2018 ◽

Vol 215 (11) ◽

pp. 2901-2918 ◽

Cited By ~ 13

Author(s):

Maria Buxadé ◽

Hector Huerga Encabo ◽

Marta Riera-Borrull ◽

Lucía Quintana-Gallardo ◽

Pilar López-Cotarelo ◽

...

Keyword(s):

Transcription Factor ◽

Immune Responses ◽

T Lymphocyte ◽

Cell Type ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Cell Type Specific ◽

Antigen Presenting ◽

Mhcii Expression

MHCII in antigen-presenting cells (APCs) is a key regulator of adaptive immune responses. Expression of MHCII genes is controlled by the transcription coactivator CIITA, itself regulated through cell type–specific promoters. Here we show that the transcription factor NFAT5 is needed for expression of Ciita and MHCII in macrophages, but not in dendritic cells and other APCs. NFAT5-deficient macrophages showed defective activation of MHCII-dependent responses in CD4+ T lymphocytes and attenuated capacity to elicit graft rejection in vivo. Ultrasequencing analysis of NFAT5-immunoprecipitated chromatin uncovered an NFAT5-regulated region distally upstream of Ciita. This region was required for CIITA and hence MHCII expression, exhibited NFAT5-dependent characteristics of active enhancers such as H3K27 acetylation marks, and required NFAT5 to interact with Ciita myeloid promoter I. Our results uncover an NFAT5-regulated mechanism that maintains CIITA and MHCII expression in macrophages and thus modulates their T lymphocyte priming capacity.

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Cell type identity determines transcriptomic immune responses inArabidopsis thalianaroots

10.1101/302448 ◽

2018 ◽

Cited By ~ 2

Author(s):

Charlotte Rich ◽

Marco U. Reitz ◽

Ruth Eichmann ◽

Sophie Hermann ◽

Dafyd J. Jenkins ◽

...

Keyword(s):

Immune Responses ◽

Gene Networks ◽

Crop Production ◽

Cell Type ◽

Cell Identity ◽

Molecular Pattern ◽

Cell Immunity ◽

Protection Strategies ◽

A Cell ◽

Cell Type Specific

AbstractRoot pathogens are a major threat in global crop production and protection strategies are required to sustainably enhance the efficiency of root immunity. Our understanding of root immunity is still limited relative to our knowledge of immune responses in leaves. In an effort to reveal the organisation of immunity in roots, we undertook a cell type-specific transcriptome analysis to identify gene networks activated in epidermis, cortex and pericycle cells ofArabidopsisroots upon treatment with two immunity elicitors, the bacterial microbe-associated molecular pattern flagellin, and the endogenous damage-associated molecular pattern Pep1. Our analyses revealed that both elicitors induced immunity gene networks in a cell type-specific manner. Interestingly, both elicitors did not alter cell identity-determining gene networks. Using sophisticated paired motif promoter analyses, we identified key transcription factor pairs involved in the regulation of cell type-specific immunity networks. In addition, our data show that cell identity networks integrate with cell immunity networks to activate cell type-specific immune response according to the functional capabilities of each cell type.Material Distribution FootnoteThe author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantcell.org) is: Patrick Schäfer ([email protected]).

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Spatially Restricted Immune Responses Allow for Root Meristematic Activity During Bacterial Colonisation

10.1101/2020.08.03.233817 ◽

2020 ◽

Cited By ~ 1

Author(s):

Aurélia Emonet ◽

Feng Zhou ◽

Jordan Vacheron ◽

Clara Margot Heiman ◽

Valérie Dénervaud Tendon ◽

...

Keyword(s):

Immune Responses ◽

Plant Immunity ◽

Central Zone ◽

Cell Type ◽

Specific Expression ◽

Molecular Pattern ◽

Cell Type Specific Expression ◽

Meristematic Activity ◽

Weak Points ◽

Cell Type Specific

SummaryPlants circumscribe microbe-associated molecular pattern (MAMP)-triggered immune responses to weak points of the roots. This spatially restricted immunity was suggested to avoid constitutive responses to rhizosphere microbiota. To demonstrate its relevance, we combined cell-type specific expression of the plant flagellin receptor (FLS2) with fluorescent defence markers and mapped immune competency at cellular resolution. Our analysis distinguishes cell-autonomous and non-cell autonomous responses and reveals lignification to be tissue-independent, contrasting cell-type specific suberisation. Importantly, our analysis divides the non-responsive meristem into a central zone refractory to FLS2 expression, and a cortex that becomes highly sensitised by FLS2 expression, causing meristem collapse upon MAMP exposure. Meristematic epidermal expression generates super-competent lines that detect native bacterial flagellin and bypass the absence of response to commensals, providing a powerful tool for studying root immunity. Our precise manipulations and read-outs demonstrate incompatibility of meristematic activity and defence and the importance of cell-resolved studies of plant immunity.

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Polyelectrolyte Coating of Ferumoxytol Differentially Impacts on Labeling of Inflammatory and Steady-State Dendritic Cell Subtypes

10.1101/2021.05.27.445994 ◽

2021 ◽

Author(s):

Nehar Celikkin ◽

John E. Wong ◽

Martin Zenke ◽

Thomas Hieronymus

Keyword(s):

Steady State ◽

Immune Responses ◽

Transplant Rejection ◽

Specific Treatment ◽

Cellular Responses ◽

Cell Type ◽

Adaptive Immune ◽

Inflammatory Conditions ◽

Cell Type Specific ◽

The Impact

Engineered magnetic nanoparticles (MNPs) are emerging as advanced tools for medical applications. The coating of MNPs using polyelectrolytes (PEs) is a versatile means to tailor MNP properties and is used to optimize MNP functionality. Dendritic cells (DCs) are critical regulators of adaptive immune responses. Functional distinct DC subsets exist either under steady-state or inflammatory conditions, which are explored for the specific treatment of various diseases, such as cancer, autoimmunity or transplant rejection. Here, the impact of PE coating of ferumoxytol for uptake into both inflammatory and steady-state DCs and cellular responses to the MNP labeling is addressed. Labeling efficiency by uncoated and PE-coated ferumoxytol is highly variable in different DC subsets, and PE coating significantly improves the labeling of steady-state DCs. Uncoated ferumoxytol results in increased cytotoxicity of steady-state DCs after labeling that is abolished by the PE coating, while no increased cell death is observed in inflammatory DCs. Furthermore, uncoated and PE-coated ferumoxytol appears immunologically inert in inflammatory DCs but induces activation of steady-state DCs. These results show that PE coating of MNPs can be applied to endow particles with desired properties for enhanced uptake and cell type-specific responses in distinct target DC populations.

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