scholarly journals MicroRNA-33–dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis

2015 ◽  
Vol 125 (12) ◽  
pp. 4334-4348 ◽  
Author(s):  
Mireille Ouimet ◽  
Hasini N. Ediriweera ◽  
U. Mahesh Gundra ◽  
Frederick J. Sheedy ◽  
Bhama Ramkhelawon ◽  
...  
2005 ◽  
Vol 17 (1) ◽  
pp. 77-86 ◽  
Author(s):  
S MANES ◽  
C GOMEZMOUTON ◽  
R LACALLE ◽  
S JIMENEZBARANDA ◽  
E MIRA ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 127 ◽  
Author(s):  
Andrea Papait ◽  
Elsa Vertua ◽  
Marta Magatti ◽  
Sabrina Ceccariglia ◽  
Silvia De Munari ◽  
...  

Placenta-derived mesenchymal stromal cells (MSC) have attracted more attention for their immune modulatory properties and poor immunogenicity, which makes them suitable for allogeneic transplantation. Although MSC isolated from different areas of the placenta share several features, they also present significant biological differences, which might point to distinct clinical applications. Hence, we compared cells from full term placenta distinguishing them on the basis of their origin, either maternal or fetal. We used cells developed by Pluristem LTD: PLacenta expanded mesenchymal-like adherent stromal cells (PLX), maternal-derived cells (PLX-PAD), fetal-derived cells (PLX-R18), and amniotic membrane-derived MSC (hAMSC). We compared immune modulatory properties evaluating effects on T-lymphocyte proliferation, expression of cytotoxicity markers, T-helper and T-regulatory cell polarization, and monocyte differentiation toward antigen presenting cells (APC). Furthermore, we investigated cell immunogenicity. We show that MSCs and MSC-like cells from both fetal and maternal sources present immune modulatory properties versus lymphoid (T cells) and myeloid (APC) cells, whereby fetal-derived cells (PLX-R18 and hAMSC) have a stronger capacity to modulate immune cell proliferation and differentiation. Our results emphasize the importance of understanding the cell origin and characteristics in order to obtain a desired result, such as modulation of the inflammatory response that is critical in fostering regenerative processes.


Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 419 ◽  
Author(s):  
Rachel H. Koh ◽  
Yinji Jin ◽  
Jisoo Kim ◽  
Nathaniel S. Hwang

Osteoarthritis (OA) is the most common form of the joint disease associated with age, obesity, and traumatic injury. It is a disabling degenerative disease that affects synovial joints and leads to cartilage deterioration. Despite the prevalence of this disease, the understanding of OA pathophysiology is still incomplete. However, the onset and progression of OA are heavily associated with the inflammation of the joint. Therefore, studies on OA treatment have sought to intra-articularly deliver anti-inflammatory drugs, proteins, genes, or cells to locally control inflammation in OA joints. These therapeutics have been delivered alone or increasingly, in delivery vehicles for sustained release. The use of hydrogels in OA treatment can extend beyond the delivery of anti-inflammatory components to have inherent immunomodulatory function via regulating immune cell polarization and activity. Currently, such immunomodulatory biomaterials are being developed for other applications, which can be translated into OA therapy. Moreover, anabolic and proliferative levels of OA chondrocytes are low, except initially, when chondrocytes temporarily increase anabolism and proliferation in response to structural changes in their extracellular environment. Therefore, treatments need to restore matrix protein synthesis and proliferation to healthy levels to reverse OA-induced damage. In conjugation with injectable and/or adhesive hydrogels that promote cartilage tissue regeneration, immunomodulatory tissue engineering solutions will have robust potential in OA treatment. This review describes the disease, its current and future immunomodulatory therapies as well as cartilage-regenerative injectable and adhesive hydrogels.


Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 700 ◽  
Author(s):  
Lucchino ◽  
Spinelli ◽  
Iannuccelli ◽  
Guzzo ◽  
Conti ◽  
...  

Mucosal surfaces play a central role in the pathogenesis of rheumatoid arthritis (RA). Several risk factors, such as cigarette smoking, environmental pollution, and periodontitis interact with the host at the mucosal level, triggering immune system activation. Moreover, the alteration of microbiota homeostasis is gaining increased attention for its involvement in the disease pathogenesis, modulating the immune cell response at a local and subsequently at a systemic level. Currently, the onset of the clinical manifest arthritis is thought to be the last step of a series of pathogenic events lasting years. The positivity for anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF), in absence of symptoms, characterizes a preclinical phase of RA—namely systemic autoimmune phase- which is at high risk for disease progression. Several immune abnormalities, such as local ACPA production, increased T cell polarization towards a pro-inflammatory phenotype, and innate immune cell activation can be documented in at-risk subjects. Many of these abnormalities are direct consequences of the interaction between the environment and the host, which takes place at the mucosal level. The purpose of this review is to describe the humoral and cellular immune abnormalities detected in subjects at risk of RA, highlighting their origin from the mucosa–environment interaction.


2015 ◽  
Vol 17 (suppl 5) ◽  
pp. v94.2-v94
Author(s):  
John Liu ◽  
Elizabeth Di Lullo ◽  
Martina Malatesta ◽  
Gary Kohanbash ◽  
Brandyn Castro ◽  
...  

ACS Omega ◽  
2021 ◽  
Vol 6 (5) ◽  
pp. 3847-3857
Author(s):  
Khaga R. Neupane ◽  
J. Robert McCorkle ◽  
Timothy J. Kopper ◽  
Jourdan E. Lakes ◽  
Surya P. Aryal ◽  
...  

2021 ◽  
Vol 22 (23) ◽  
pp. 13156
Author(s):  
Patrick Klüber ◽  
Steffen K. Meurer ◽  
Jessica Lambertz ◽  
Roman Schwarz ◽  
Silke Zechel-Gran ◽  
...  

Lipocalin 2 (LCN2) mediates key roles in innate immune responses. It has affinity for many lipophilic ligands and binds various siderophores, thereby limiting bacterial growth by iron sequestration. Furthermore, LCN2 protects against obesity and metabolic syndrome by interfering with the composition of gut microbiota. Consequently, complete or hepatocyte-specific ablation of the Lcn2 gene is associated with higher susceptibility to bacterial infections. In the present study, we comparatively profiled microbiota in fecal samples of wild type and Lcn2 null mice and show, in contrast to previous reports, that the quantity of DNA in feces of Lcn2 null mice is significantly lower than that in wild type mice (p < 0.001). By using the hypervariable V4 region of the 16S rDNA gene and Next-Generation Sequencing methods, we found a statistically significant change in 16 taxonomic units in Lcn2-/- mice, including eight gender-specific deviations. In particular, members of Clostridium, Escherichia, Helicobacter, Lactococcus, Prevotellaceae_UCG-001 and Staphylococcus appeared to expand in the intestinal tract of knockout mice. Interestingly, the proportion of Escherichia (200-fold) and Staphylococcus (10-fold) as well as the abundance of intestinal bacteria encoding the LCN2-sensitive siderphore enterobactin (entA) was significantly increased in male Lcn2 null mice (743-fold, p < 0.001). This was accompanied by significant higher immune cell infiltration in the ileum as demonstrated by increased immunoreactivity against the pan-leukocyte protein CD45, the lymphocyte transcription factor MUM-1/IRF4, and the macrophage antigen CD68/Macrosialin. In addition, we found a higher expression of mucosal mast cell proteases indicating a higher number of those innate immune cells. Finally, the ileum of Lcn2 null mice displayed a high abundance of segmented filamentous bacteria, which are intimately associated with the mucosal cell layer, provoking epithelial antimicrobial responses and affecting T-helper cell polarization.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shuyue Wang ◽  
Kun Xie ◽  
Tengfei Liu

The immunotherapeutic treatment of various cancers with an increasing number of immune checkpoint inhibitors (ICIs) has profoundly improved the clinical management of advanced diseases. However, just a fraction of patients clinically responds to and benefits from the mentioned therapies; a large proportion of patients do not respond or quickly become resistant, and hyper- and pseudoprogression occur in certain patient populations. Furthermore, no effective predictive factors have been clearly screened or defined. In this review, we discuss factors underlying the elucidation of potential immunotherapeutic resistance mechanisms and the identification of predictive factors for immunotherapeutic responses. Considering the heterogeneity of tumours and the complex immune microenvironment (composition of various immune cell subtypes, disease processes, and lines of treatment), checkpoint expression levels may not be the only factors underlying immunotherapy difficulty and resistance. Researchers should consider the tumour microenvironment (TME) landscape in greater depth from the aspect of not only immune cells but also the tumour histology, molecular subtype, clonal heterogeneity and evolution as well as micro-changes in the fine structural features of the tumour area, such as myeloid cell polarization, fibroblast clusters and tertiary lymphoid structure formation. A comprehensive analysis of the immune and molecular profiles of tumour lesions is needed to determine the potential predictive value of the immune landscape on immunotherapeutic responses, and precision medicine has become more important.


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