Fa(c)t checking: How fatty acids shape metabolism and function of macrophages and dendritic cells

In many subjects who are genetically susceptible to asthma, exposure to environmental stimuli may exacerbate their condition. However, it is unknown how the expression and function of a family of pattern-recognition receptors called toll-like receptors (TLR) are affected by exposure to particulate pollution. TLRs serve a critical function in alerting the immune system of tissue damage or infection—the so-called “danger signals”. We are interested in the role that TLRs play in directing appropriate responses by innate immunity, particularly dendritic cells (DC), after exposing them to particulate pollution. Dendritic cells serve a pivotal role in directing host immunity. Thus, we hypothesized that alterations in TLR expression could be further explored as potential biomarkers of effect related to DC exposure to particulate pollution. We show some preliminary data that indicates that inhaled particulate pollution acts directly on DC by down-regulating TLR expression and altering the activation state of DC. While further studies are warranted, we suggest that alterations in TLR2 and TLR4 expression should be explored as potential biomarkers of DC exposure to environmental particulate pollution.

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B lymphocytes can regulate the maturation and function of human dendritic cells but are partially inefficient in systemic lupus erythematosus

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2011-201234.6 ◽

2012 ◽

Vol 71 (Suppl 1) ◽

pp. A34.1-A34

Author(s):

Ahsen Morva ◽

Sébastien Lemoine ◽

Achouak Achour ◽

Alain Saraux ◽

Jacques-Olivier Pers ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Dendritic Cells ◽

B Lymphocytes ◽

Lupus Erythematosus ◽

Systemic Lupus ◽

And Function ◽

Human Dendritic Cells

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NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22115902 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5902

Author(s):

Stefan Nagel ◽

Claudia Pommerenke ◽

Corinna Meyer ◽

Hans G. Drexler

Keyword(s):

Dendritic Cells ◽

Transcription Factors ◽

Cell Lines ◽

Expression Profiling ◽

Regulatory Network ◽

Homeobox Gene ◽

Leukemia Cell Line ◽

Specific Gene ◽

Rna Seq ◽

And Function

Recently, we documented a hematopoietic NKL-code mapping physiological expression patterns of NKL homeobox genes in human myelopoiesis including monocytes and their derived dendritic cells (DCs). Here, we enlarge this map to include normal NKL homeobox gene expressions in progenitor-derived DCs. Analysis of public gene expression profiling and RNA-seq datasets containing plasmacytoid and conventional dendritic cells (pDC and cDC) demonstrated HHEX activity in both entities while cDCs additionally expressed VENTX. The consequent aim of our study was to examine regulation and function of VENTX in DCs. We compared profiling data of VENTX-positive cDC and monocytes with VENTX-negative pDC and common myeloid progenitor entities and revealed several differentially expressed genes encoding transcription factors and pathway components, representing potential VENTX regulators. Screening of RNA-seq data for 100 leukemia/lymphoma cell lines identified prominent VENTX expression in an acute myelomonocytic leukemia cell line, MUTZ-3 containing inv(3)(q21q26) and t(12;22)(p13;q11) and representing a model for DC differentiation studies. Furthermore, extended gene analyses indicated that MUTZ-3 is associated with the subtype cDC2. In addition to analysis of public chromatin immune-precipitation data, subsequent knockdown experiments and modulations of signaling pathways in MUTZ-3 and control cell lines confirmed identified candidate transcription factors CEBPB, ETV6, EVI1, GATA2, IRF2, MN1, SPIB, and SPI1 and the CSF-, NOTCH-, and TNFa-pathways as VENTX regulators. Live-cell imaging analyses of MUTZ-3 cells treated for VENTX knockdown excluded impacts on apoptosis or induced alteration of differentiation-associated cell morphology. In contrast, target gene analysis performed by expression profiling of knockdown-treated MUTZ-3 cells revealed VENTX-mediated activation of several cDC-specific genes including CSFR1, EGR2, and MIR10A and inhibition of pDC-specific genes like RUNX2. Taken together, we added NKL homeobox gene activities for progenitor-derived DCs to the NKL-code, showing that VENTX is expressed in cDCs but not in pDCs and forms part of a cDC-specific gene regulatory network operating in DC differentiation and function.

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Cellular and metabolic mechanisms of nutrient actions in immune function

Nutrition and Diabetes ◽

10.1038/s41387-021-00162-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Philip Newsholme

Keyword(s):

Amino Acids ◽

Fatty Acids ◽

Vitamin D ◽

Immune System ◽

Cell Function ◽

Immune Cell ◽

Cell Structure ◽

Nutritional Intervention ◽

Immune Cell Function ◽

And Function

AbstractVarious nutrients can change cell structure, cellular metabolism, and cell function which is particularly important for cells of the immune system as nutrient availability is associated with the activation and function of diverse immune subsets. The most important nutrients for immune cell function and fate appear to be glucose, amino acids, fatty acids, and vitamin D. This perspective will describe recently published information describing the mechanism of action of prominent nutritional intervention agents where evidence exists as to their action and potency.

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