Primary Sjögren\'s disease is primarily driven by B-cell activation and is associated with a high risk of developing non-Hodgkin\'s lymphoma (NHL). Over the last few decades, microRNA-155 (miR-155) has arisen as a key regulator of B-cells. Nevertheless, its role in primary Sjögren\'s disease remains elusive. Thus, the purpose of this study was (i) to explore miR-155, B-cell activating factor (BAFF)-receptor (BAFF-R), and Interleukin 6 receptor (IL-6R) expression in the labial salivary glands (LSG) of patients with primary Sjögren\'s disease, aiming to identify potential B-cell activation biomarkers related to NHL development. Twenty-four patients with primary Sjögren\'s disease, and with available tissue blocks from a LSG biopsy performed at diagnosis, were enrolled. Among them, five patients developed B-cell NHL during follow-up (7.3 ± 3.1 years). A comparison group of 20 individuals with sicca disease was included. Clinical and laboratory parameters were recorded and the LSG biopsies were evaluated to assess local inflammation in terms of miR-155/BAFF-R and IL-6R expression. Stratifying the primary Sjögren\'s disease cohort according to lymphomagenesis, miR-155 was upregulated in primary Sjögren\'s disease patients who experienced NHL, more so than those who did not experience NHL. Moreover, miR-155 expression correlated with the focus score (FS), as well as BAFF-R and IL-6R expression, which were increased in primary Sjögren\'s disease patients and in turn related to neoplastic evolution. In conclusion, epigenetic modulation may play a crucial role in the aberrant activation of B-cells in primary Sjögren\'s disease, profoundly impacting the risk of NHL development.

UNASSIGNED: Group 2 innate lymphoid cells (ILC2s) have been found to take part in type 2 inflammation by secreting TH2 cytokines. Apolipoprotein A-I (Apo-AI), a major structural and functional protein of high-density lipoproteins, has anti-inflammatory effects on neutrophils, monocytes, macrophages, and eosinophils. However, its effects on ILC2s are not well characterized.
UNASSIGNED: We aimed to investigate the effect of Apo-AI on the proliferation and function of ILC2s as well as its possible mechanism.
UNASSIGNED: The protein expression of Apo-AI and the percentage of ILC2s in peripheral blood between 20 allergic rhinitis patients and 20 controls were detected by ELISA and flow cytometry. The effect of Apo-AI and miR-155 on ILC2 proliferation and function was detected by tritiated thymidine incorporation and ELISA. Anima models were adopted to verify the effect of Apo-AI in vivo.
UNASSIGNED: Elevated expression of Apo-AI was observed in allergic rhinitis patients. Apo-AI promotes ABCA1 expression by ILC2s, which can be inhibited by anti-Apo-AI. Apo-AI decreased ILC2 proliferation and the microRNA levels of GATA3 and RORα from ILC2s. The miR-155 overexpression promoted the upregulation of GATA3 and type II cytokines from ILC2s, while the addition of Apo-AI or miR-155 inhibitor significantly inhibited expression of GATA3 and type II cytokines by ILC2s. Apo-AI-/- mice showed as enhanced allergen-induced airway inflammation. The miR-155 inhibitor can reverse the enhanced allergen-induced airway inflammation in Apo-AI-/- mice, while miR-155 mimics can reverse the decreased allergen-induced airway inflammation in Apo-AI-treated mice.
UNASSIGNED: Apo-AI suppressed the proliferation and function of ILC2s through miR-155 in allergic rhinitis. Our data provide new insights into the mechanism of allergen-induced airway inflammation.

Atopic dermatitis (AD) is a common inflammatory skin condition and the leading cause of morbidity associated with skin conditions worldwide. For the majority of patients, AD is a lifelong disease that cannot be cured completely. Therefore, in the present study, differentially expressed genes (DEGs) in the epidermal immune microenvironment were screened using bioinformatic techniques. Subsequently, an in vitro cellular model was constructed to investigate the role of microRNA (miR)-155 in immune infiltration during AD. In the present study, two datasets (GSE121212 and GSE157194) were downloaded from Gene Expression Omnibus, before the DEGs were screened and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses. miRNet was used to predict the possible target genes of miR-155 among the differentially expressed genes found. Consequently, peptidase inhibitor 3 (PI3), FOS-like 1, AP-1 transcription factor subunit (FOSL1), C-X-C motif chemokine ligand (CXCL)1 and CXCL8 were selected to be the potential target genes of miR-155 in the epidermal immune microenvironment of patients with AD. Concurrently, an inflammatory cell model using HaCaT cells was constructed by TNF-α and IFN-γ treatment. The effects of miR-155 on HaCaT cell proliferation and secretion of IL-1β, IL-6, IL-10, IL-15, PI3, FOSL1, CXCL1 and CXCL8 under inflammatory and non-inflammatory conditions were then analyzed. The results showed that after the HaCaT cells were transfected with miR-155, miR-155 inhibited HaCaT cell proliferation and decreased the mRNA expression levels of PI3 and CXCL8, increased the mRNA levels of FOSL1 and secretion levels of IL-1β, IL-6, IL-15 and CXCL1. By contrast, miR-155 decreased the secretion levels of IL-10 and CXCL8. In the inflammatory cell model of HaCaT cells, miR-155 was found to significantly inhibit the proliferation of HaCaT cells during inflammation whilst significantly increasing the secretion of IL-1β, IL-6, IL-10 and IL-15. In addition, miR-155 increased the mRNA expression and secretion levels of CXCL1 and CXCL8, whilst also increasing the mRNA expression levels of PI3. Results from the current study suggest that miR-155 can stimulate keratinocytes to produce inflammatory cytokines and proteins to enhance the inflammatory response in AD.

MicroRNA-155 (miR-155) is a multifunctional miRNA whose expression is known to be involved in a range of physiological and pathological processes. Its association with several oral diseases has been established. However, the specific role of miR-155 in orthodontic tooth movement remains unclear. In this study, we investigated the impact of miR-155 on osteoclast differentiation and orthodontic tooth movement models, aiming to explore the underlying mechanisms.
In this experiment, we utilized various agents including miR-155 mimic, miR-155 inhibitor, as well as non-specific sequences (NC mimic & NC inhibitor) to treat murine BMMNCs. Subsequently, osteoclast induction (OC) was carried out to examine the changes in the differentiation ability of monocytes under different conditions. To assess these changes, we employed RT-PCR, Western blotting, and TRAP staining techniques. For the orthodontic tooth movement model in mice, the subjects were divided into two groups: the NaCl group (injected with saline solution) and the miR-155 inhibitor group (injected with AntagomiR-155). We observed the impact of orthodontic tooth movement using stereoscopic microscopy, micro-CT, and HE staining. Furthermore, we performed RT-PCR and Western blotting analyses on the tissues surrounding the moving teeth. Additionally, we employed TargetScan to predict potential target genes of miR-155.
During osteoclast induction of BMMNCs, the expression of miR-155 exhibited an inverse correlation with osteoclast-related markers. Overexpression of miR-155 led to a decrease in osteoclast-related indexes, whereas underexpression of miR-155 increased those indexes. In the mouse orthodontic tooth movement model, the rate of tooth movement was enhanced following injection of the miR-155 inhibitor, leading to heightened osteoclast activity. TargetScan analysis identified SOCS1 as a target gene of miR-155.
Our results suggest that miR-155 functions as an inhibitor of osteoclast differentiation, and it appears to regulate osteoclasts during orthodontic tooth movement. The regulatory mechanism of miR-155 in this process involves the targeting of SOCS1.

UNASSIGNED: Autophagy has been proven to contribute to maintaining eukaryotic cells\' normal intracellular homeostasis, whereas autophagy malfunction may predispose to Behcet Disease (BD). The accumulation of the products of autophagic degradation as well as impairment in autophagic flux in cases with BD, may be attributed to dysregulated miRNA-155 expression. This study attempts to determine the contribution of circRNA-0067835 in miRNA-155-mediated modulation of the autophagy axis as well as to investigate its impact on the production of pro-inflammatory cytokines in BD.
UNASSIGNED: This study was carried out on 40 cases with BD and 40 healthy control subjects. The collection of serum samples was done before performing a real-time PCR to estimate the relative gene expression of ATG1, AKT, miRNA-155, mTOR, TAB2, and circRNA-0067835. Additionally, IL-1β, IL-17, and TNF-α serum levels were determined by ELISA.
UNASSIGNED: Behcet Disease (BD) patients had significantly upregulated circRNA-0067835, with subsequent downregulation of its target gene, miRNA-155 than controls (P<0.05). In addition, decreased miRNA-155 gene expression was correlated with significantly increased TAB2 gene expression levels in BD patients compared to the controls (P<0.05). Furthermore, enhanced production of pro-inflammatory cytokines was detected in cases with BD than in controls.
UNASSIGNED: The correlation between circRNA-0067835 and miRNA-155 fairly contributes to the regulation of cytokine production in BD via the modulation of autophagy. The investigation of the circRNA-0067835 and the microRNA-155 and their downstream adaptor molecules could be a potential therapeutic agent for BD.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection in the young and healthy usually results in an asymptomatic or mild viral syndrome, possibly through an erythropoietin (EPO)-dependent, protective evolutionary landscape. In the old and in the presence of co-morbidities, however, a potentially lethal coronavirus disease 2019 (COVID-19) cytokine storm, through unrestrained renin-angiotensin aldosterone system (RAAS) hyperactivity, has been described. Multifunctional microRNA-155 (miR-155) elevation in malaria, dengue virus (DENV), the thalassemias, and SARS-CoV-1/2, plays critical antiviral and cardiovascular roles through its targeted translational repression of over 140 genes. In the present review, we propose a plausible miR-155-dependent mechanism whereby the translational repression of AGRT1, Arginase-2 and Ets-1, reshapes RAAS towards Angiotensin II (Ang II) type 2 (AT2R)-mediated balanced, tolerable, and SARS-CoV-2-protective cardiovascular phenotypes. In addition, it enhances EPO secretion and endothelial nitric oxide synthase activation and substrate availability, and negates proinflammatory Ang II effects. Disrupted miR-155 repression of AT1R + 1166C-allele, significantly associated with adverse cardiovascular and COVID-19 outcomes, manifests its decisive role in RAAS modulation. BACH1 and SOCS1 repression creates an anti-inflammatory and cytoprotective milieu, robustly inducing antiviral interferons. MiR-155 dysregulation in the elderly, and in comorbidities, allows unimpeded RAAS hyperactivity to progress towards a particularly aggressive COVID-19 course. Elevated miR-155 in thalassemia plausibly engenders a favorable cardiovascular profile and protection against malaria, DENV, and SARS-CoV-2. MiR-155 modulating pharmaceutical approaches could offer novel therapeutic options in COVID-19.

Objective: Chronic rejection remains the main factor that influence long-term survival of patients after heart transplantation. Interleukin-10 (IL-10) play critical role in macrophages-mediated transplant immune responses. We investigated the mechanism of IL-10 in macrophage related chronic rejection after mouse heart transplantation. Methods: Mouse heart transplant chronic rejection model was established to evaluate pathological changes in the allograft. Myocardial interstitial fibrosis, apoptosis, and inflammatory factor levels were detected in ad-IL-10-treated mice. The positive iNOS+ and Arg-1+ expressions, macrophage subset changes, and the proportion of regulatory T-cells (Tregs) and TIGIT+ Tregs were quantified by flow. In in vitro experiments, ad-IL-10 was transfected into macrophages followed by detection of apoptosis, phagocytosis, and CD163, CD16/32, and CD206 expression. The expression and relationships between IL-10, miR-155, and SOCS5 were also detected and verified. A rescue experiment was performed to evaluate macrophage function through the combined treatment of ad-IL-10 and overexpression of miR-155. Results: Significantly decreased IL-10 expression in chronic rejection during mouse heart transplantation was observed. Ad-IL-10-treated mice showed decreased pathological injury, perivascular fibrosis, apoptosis, inflammation, and iNOS+ and CD16/32+ expression, and increased Treg/TIGIT+ Treg cell, Arg-1+ and CD206+ cell proportion. Ad-IL-10-treated macrophages in vitro showed reduced apoptosis, improved phagocytosis, and M2 polarization. Mechanically, IL-10 negatively regulated miR-155 to activate SOCS5. Overexpression of miR-155 reversed IL-10 mediated-positive regulation of macrophage function. Conclusion: IL-10 downregulated miR-155 and activated SOCS5, thereby promoting macrophage M2 polarization to relieve chronic rejection after heart transplantation.

OBJECTIVE: To identify a panel of potential biomarkers consisting of microRNA-155 (miR-155), tumor necrosis factor-alpha (TNF-α), interleukin-37 (IL-37) for the diagnosis of active pulmonary tuberculosis (PTB) infection in elderly patients.
METHODS: The serum expression of miR-155 and TNF-α in patients was measured by RT-qPCR, and the serum IL-37 level was determined by ELISA. The correlation between their expression and the features of active PTB patients was also analyzed. The AUCs of miR-155, TNF-α and IL-37 in diagnosing active PTB was calculated according to the ROC curves. The sensitivity, specificity and Youden\'s index of the three biomarkers alone or in combination for the active PTB diagnosis in the elderly were assessed.
RESULTS: miR-155, TNF-α, and IL-37 were overexpressed in the sera of elderly patients with active PTB. miR-155, TNF-α and IL-37 serum levels were enhanced in the elderly patients with pulmonary and extrapulmonary TB relative to those with PTB only, and in patients with active TB infection in both lungs compared to those with unilateral lung infection. The AUCs of miR-155, TNF-α and IL-37 for the diagnosis of active PTB were 0.7920, 0.8734 and 0.7398, respectively. The combination of these three improved the sensitivity of the diagnosis (84.78%).
CONCLUSIONS: miR-155, TNF-α and IL-37 were overexpressed in elderly patients with active PTB. The combined detection of serum miR-155/TNF-α/IL-37 expression has potential to serve as a diagnostic tool for active PTB in the elderly.

OBJECTIVE: Corneal endothelial cells (CECs) are extremely vulnerable to injury. In this study, the role and mechanism of action of the long non-coding RNA HOXA11-AS during corneal endothelial injury (CEI) were evaluated in vivo and in vitro.
METHODS: Scratch wounds were made to induce CEI in the corneal endothelium of rats and mice. Homeobox A11 (HOXA11)-AS expression was determined at different time points using quantitative real-time PCR. Human CECs with HOXA11-AS overexpression or downregulation were examined for survival, ferroptosis, and migration. Bioinformatics and dual-luciferase reporter assays were used to investigate the correlation between HOXA11-AS and microRNA (miR)-155.
RESULTS: HOXA11-AS expression was reduced in the corneal endothelium in a time-dependent manner. Scratch wounds triggered high rates of ferroptosis and migration in CECs and impaired cell proliferation. HOXA11-AS overexpression partially attenuated the scratch wound-induced changes in proliferation, ferroptosis, and migration, whereas silencing HOXA11-AS had the opposite effects. Moreover, HOXA11-AS served as a competing endogenous RNA of miR-155. Levels of miR-155 were upregulated in the corneal endothelium following the scratch injury, and this upregulation abolished the effect of HOXA11-AS overexpression on the behavior of CECs after injury; miR-155 inhibition counteracted the effect of HOXA11-AS silencing.
CONCLUSIONS: HOXA11-AS exerts protective effects against CEI by sponging miR-155, suggesting that these loci are treatment targets for corneal endothelial disorders.

miRNA155 (miR155) has emerged as an important regulator of breast cancer (BrCa) development. Studies have consistently noted an increase in miR155 levels in serum and/or tissues in patients with BrCa. However, what is less clear is whether this increase in miR155 is a reflection of oncogenic or tumor suppressive properties. To study the effects of miR155 in a transgenic model of BrCA, we developed an MMTV-PyMT mouse deficient in miR155 (miR155-/- PyMT). miR155-/- mice (n = 11) exhibited reduced tumor number and volume palpations at ∼14-18 wk of age compared with miR155 sufficient littermates (n = 12). At 19 wk, mammary glands were excised from tumors for RT-PCR, and tumors were counted, measured, and weighed. miR155-/- PyMT mice exhibited reduced tumor volume, number, and weight, which was confirmed by histopathological analysis. There was an increase in apoptosis with miR155 deficiency and a decrease in proliferation. As expected, miR155 deficiency resulted in upregulated gene expression of suppressor of cytokine signaling 1 (Socs1)-its direct target. There was a reduction in gene expression of macrophage markers (CD68, Adgre1, Itgax, Mrc1) with miR-155-/- and this was confirmed with immunofluorescence staining for F4/80. miR155-/- increased expression of M1 macrophage marker Nos2 and reduced expression of M2 macrophage markers IL-10, IL-4, Arg1, and MMP9. Overall, miR155 deficiency reduced BrCA and improved the tumor microenvironment through the reduction of genes associated with protumorigenic processes. However, given the inconsistencies in the literature, additional studies are needed before any attempts are made to harness miR155 as a potential oncogenic or tumor suppressive miRNA.NEW & NOTEWORTHY To examine the effects of miR155 in a transgenic model of breast cancer, we developed an MMTV-PyMT mouse-deficient in miR155. We demonstrate that global loss of miR155 resulted in blunted tumor growth through modulating the tumor microenvironment. Specifically, miR155-deficient mice had smaller and less invasive tumors, an increase in apoptosis and a decrease in proliferation, a reduction in tumor-associated macrophages, and the expression of genes associated with protumoral processes.