Macrophages contribute to the pathogenesis of rheumatoid arthritis (RA). They can display different states of activation or "polarization," notably the so-called inflammatory "M1" and the various ...alternative "M2" polarizations, characterized by distinct functions. Data regarding the effects of RA anti-cytokine biological disease-modifying anti-rheumatic drugs (bDMARDs) on macrophage polarization are scarce. We aimed to assess
modulation of macrophage polarization by bDMARDs targeting pro-inflammatory cytokines in RA. We generated monocyte derived macrophages using blood samples from 20 RA patients with active RA and 30 healthy controls. We evaluated
the impact on M1 inflammatory macrophages of: etanercept (ETA), adalimumab (ADA), certolizumab (CZP), tocilizumab (TCZ), and rituximab (RTX). We assessed the impact on macrophage polarization using flow cytometry and RTqPCR to study the expression of surface markers and perform functional studies of cytokine production, phagocytosis, and negative feedback control of inflammation. Among evaluated bDMARDs, anti-TNF agents modulated the polarization of inflammatory macrophages by decreasing inflammatory surface markers (CD40, CD80) and favoring alternative markers (CD16, CD163, MerTK). Anti-TNF agents also induced alternative functions in macrophages activated in inflammatory condition with (i) the inhibition of inflammatory cytokines (TNF, IL-6, IL-12), (ii) an increase in phagocytosis. These findings were mechanistically related to an increase in early IL-10 production, responsible for higher negative feedback control of inflammation involving SOCS3 and Gas6. This IL-10 effect was STAT3-dependent. Anti-TNF agents not only inhibit
inflammatory functions of macrophages, but also favor resolution of inflammation through polarization toward alternative features specifically involving the IL-10/STAT3 axis.
Summary
In most plants, NO3− constitutes the major source of nitrogen, and its assimilation into amino acids is mainly achieved in shoots. Furthermore, recent reports have revealed that reduction of ...NO3− translocation from roots to shoots is involved in plant acclimation to abiotic stress. NPF2.3, a member of the NAXT (nitrate excretion transporter) sub‐group of the NRT1/PTR family (NPF) from Arabidopsis, is expressed in root pericycle cells, where it is targeted to the plasma membrane. Transport assays using NPF2.3‐enriched Lactococcus lactis membranes showed that this protein is endowed with NO3− transport activity, displaying a strong selectivity for NO3− against Cl−. In response to salt stress, NO3− translocation to shoots is reduced, at least partly because expression of the root stele NO3− transporter gene NPF7.3 is decreased. In contrast, NPF2.3 expression was maintained under these conditions. A loss‐of‐function mutation in NPF2.3 resulted in decreased root‐to‐shoot NO3− translocation and reduced shoot NO3− content in plants grown under salt stress. Also, the mutant displayed impaired shoot biomass production when plants were grown under mild salt stress. These mutant phenotypes were dependent on the presence of Na+ in the external medium. Our data indicate that NPF2.3 is a constitutively expressed transporter whose contribution to NO3− translocation to the shoots is quantitatively and physiologically significant under salinity.
Significance Statement
The constitutively expressed root stele transporter NPF2.3 from Arabidopsis promotes nitrate loading into the xylem sap and its contribution to nitrate allocation to shoots becomes quantitatively significant upon salt stress, which was unexpected because salinity is known to depress nitrate translocation. The loss‐of‐function mutation npf2.3 resulted in reduced biomass production when plants were grown in soil supplemented with sodium concentrations compatible with life cycle completion, indicating that NPF2.3 contributes to plant acclimation to moderate salinity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Biotherapies have revolutionized the treatment of RA. However, much work is needed to understand all the mechanisms of these biotherapies, and alternatives are needed to circumvent adverse effects ...and the high cost of these long-lasting treatments. In this article we outline some of the approaches we have used to target monocytes/macrophages as major components of inflammation and bone homeostasis. We also discuss how anti-TNF-α antibodies target monocytes/macrophages in the complex mechanisms contributing to inhibition of inflammation.
Tumor necrosis factor (TNF) is a pleiotropic cytokine involved in many aspects of immune regulation. Anti-TNF biological therapy has been considered a breakthrough in the treatment of chronic ...autoimmune diseases, such as rheumatoid arthritis (RA). In this review, because of the major involvement of T cells in RA pathogenesis, we discuss the effects of anti-TNF biotherapy on T-cell responses in RA patients. We also outline the potential fields for future research in the area of anti-TNF therapy in RA.This could be useful to better understand the therapeutic efficiency and the side effects that are encountered in RA patients. Better targeting of T cells in RA could help set more specific anti-TNF strategies and develop prediction tools for response.
Abstract Objective Rheumatoid arthritis is associated with increased cardiovascular morbidity and mortality. We performed a systematic review of the literature and a meta-analysis to look for ...differences in the prevalence of traditional cardiovascular risk factor between RA patients and controls. Methods Medline database was searched to identify studies evaluating the prevalence of traditional cardiovascular risk factors in rheumatoid arthritis patients and controls. Studies were selected and reviewed by two investigators. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated and pooled using a random-effects model. Statistical heterogeneity was evaluated through the use of Chi2 and I2 statistics. Results Fifteen case-control studies with a total of 2956 patients and 3713 controls met the inclusion criteria. The prevalence of smoking was increased in RA patients in comparison with controls: OR (95%CI) 1.56 (1.35–1.80) ( P < 0.00001). The prevalence of hypertension did not differ: OR (95% CI) 1.09 (0.91–1.31) ( P = 0.35). The prevalence of diabetes mellitus was increased in RA: OR (95%CI) 1.74 (1.22–2.50) ( P = 0.003). The prevalence of hypercholesterolemia did not differ: OR (95%CI) 0.84 (0.67–1.04) ( P = 0.11). HDL cholesterol levels were lower in RA patients: weighted mean difference −17.72 mg/dl (−18.35 – −17.08) ( P < 0.00001). Significant heterogeneity among studies was found for diabetes mellitus and HDL cholesterol levels. Conclusions Some traditional cardiovascular risk factors, such as smoking, diabetes mellitus or lower HDL cholesterol levels, appear more prevalent in rheumatoid arthritis patients and could contribute to the increased cardiovascular morbidity and mortality observed in rheumatoid arthritis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Protein acetylation is a highly frequent protein modification. However, comparatively little is known about its enzymatic machinery. N‐α‐acetylation (NTA) and ε‐lysine acetylation (KA) are known to ...be catalyzed by distinct families of enzymes (NATs and KATs, respectively), although the possibility that the same GCN5‐related N‐acetyltransferase (GNAT) can perform both functions has been debated. Here, we discovered a new family of plastid‐localized GNATs, which possess a dual specificity. All characterized GNAT family members display a number of unique features. Quantitative mass spectrometry analyses revealed that these enzymes exhibit both distinct KA and relaxed NTA specificities. Furthermore, inactivation of GNAT2 leads to significant NTA or KA decreases of several plastid proteins, while proteins of other compartments were unaffected. The data indicate that these enzymes have specific protein targets and likely display partly redundant selectivity, increasing the robustness of the acetylation process in vivo. In summary, this study revealed a new layer of complexity in the machinery controlling this prevalent modification and suggests that other eukaryotic GNATs may also possess these previously underappreciated broader enzymatic activities.
Synopsis
A novel protein acetyltransferase family localized or associated to plant plastids is identified and characterised. These GCN5‐related N‐acetyltransferases (GNATs) have unique amino acid sequence characteristics and unambiguously possess dual N‐α‐ and ε‐lysine acetylation activities.
An in silico search for putative plastidial N‐terminal and lysine acetyltransferases reveals 10 putative GNAT candidates, showing unique features both at the level of the conserved motifs and key residues.
Localization to chloroplasts is confirmed for seven of them, while another one is either associated to chloroplasts or localized within the nucleus.
All plastid‐associated GNATs display distinct lysine acetyltransferase and relaxed N‐ terminal acetyltransferase substrate specificities.
Inactivation of GNAT2, the plastid GNAT involved in photosynthetic state transitions, results in NTA decreases confined to chloroplast proteins, next to the known decreases on photosynthetic KA target proteins.
A novel protein acetyltransferase family localized or associated to plant plastids is identified and characterised. These GCN5‐related N‐acetyltransferases (GNATs) have unique amino acid sequence characteristics and unambiguously possess dual N‐α‐ and ε‐lysine acetylation activities.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
•NRT1/PTR proteins transport a wide variety of substrates.•Members of this family should be named NPF (NRT1/PTR Family).•Phylogenetic studies of 31 fully sequenced plant genomes identify eight ...subfamilies.
Members of the plant NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER (NRT1/PTR) family display protein sequence homology with the SLC15/PepT/PTR/POT family of peptide transporters in animals. In comparison to their animal and bacterial counterparts, these plant proteins transport a wide variety of substrates: nitrate, peptides, amino acids, dicarboxylates, glucosinolates, IAA, and ABA. The phylogenetic relationship of the members of the NRT1/PTR family in 31 fully sequenced plant genomes allowed the identification of unambiguous clades, defining eight subfamilies. The phylogenetic tree was used to determine a unified nomenclature of this family named NPF, for NRT1/PTR FAMILY. We propose that the members should be named accordingly: NPFX.Y, where X denotes the subfamily and Y the individual member within the species.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
10.
Looking for Root Hairs to Overcome Poor Soils Rongsawat, Thanyakorn; Peltier, Jean-Benoît; Boyer, Jean-Christophe ...
Trends in plant science,
January 2021, 2021-01-00, 20210101, 2021, Volume:
26, Issue:
1
Journal Article
Peer reviewed
Open access
Breeding new cultivars allowing reduced fertilization and irrigation is a major challenge. International efforts towards this goal focus on noninvasive methodologies, platforms for high-throughput ...phenotyping of large plant populations, and quantitative description of root traits as predictors of crop performance in environments with limited water and nutrient availability. However, these high-throughput analyses ignore one crucial component of the root system: root hairs (RHs). Here, we review current knowledge on RH functions, mainly in the context of plant hydromineral nutrition, and take stock of quantitative genetics data pointing at correlations between RH traits and plant biomass production and yield components.
Plant breeding for improved belowground traits, allowing reduced fertilization and irrigation inputs, can contribute to the development of sustainable agriculture practices.Root hairs (RHs) increase the volume of exploited soil, and have major roles in nutrient and water uptake as well as in beneficial interactions with soil microorganisms.Plant engagement in mycorrhizal symbiosis also increases the volume of exploited soil, but appears less efficient than RH development in terms of biomass production in some soil conditions.Evidence that plant biomass production can be positively correlated to RH length is available.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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