scholarly journals Innate Signaling in the CNS Prevents Demyelination in a Focal EAE Model

2021 ◽  
Vol 15 ◽  
Author(s):  
Magdalena Dubik ◽  
Joanna Marczynska ◽  
Marlene T. Mørch ◽  
Gill Webster ◽  
Kirstine Nolling Jensen ◽  
...  
Keyword(s):  
Interleukin 10 ◽  
Needle Insertion ◽  
Protective Role ◽  
Type I ◽  
Focal Lesions ◽  
Cervical Lymph Nodes ◽  
Arginase 1 ◽  
Demyelinating Lesions ◽  
Eae Model ◽  
Cns Stimulation

The pathological hallmark of multiple sclerosis (MS) is the formation of multifocal demyelinating lesions in the central nervous system (CNS). Stimulation of innate receptors has been shown to suppress experimental autoimmune encephalomyelitis (EAE), an MS-like disease in mice. Specifically, targeting Toll-like receptor 9 (TLR9) and NOD-like receptor 2 (NOD2) significantly reduced disease severity. In the present work we have developed a novel focal EAE model to further study the effect of innate signaling on demyelinating pathology. Focal lesions were induced by stereotactic needle insertion into the corpus callosum (CC) of mice previously immunized for EAE. This resulted in focal pathology characterized by infiltration and demyelination in the CC. We find that intrathecal delivery of MIS416, a TLR9 and NOD2 bispecific innate ligand, into the cerebrospinal fluid reduced focal lesions in the CC. This was associated with upregulation of type I and II interferons, interleukin-10, arginase-1, CCL-2 and CXCL-10. Analysis of draining cervical lymph nodes showed upregulation of type II interferons and interleukin 10. Moreover, intrathecal MIS416 altered the composition of early CNS infiltrates, increasing proportions of myeloid and NK cells and reducing T cells at the lesion site. This study contributes to an increased understanding of how innate immune responses can play a protective role, which in turn may lead to additional therapeutic strategies for the prevention and treatment of demyelinating pathologies.

P0523PROTECTIVE ROLE OF REGULATORY B CELLS ON THE RENAL TISSUE REPAIRMEN AFTER ISCHEMIA REPERCUSSION INJURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yokota Yunosuke ◽  
Goh Kodama ◽  
Sakuya Itou ◽  
Yosuke Nakayama ◽  
Nobukazu Komatsu ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Renal Function ◽  
B Cells ◽  
Interleukin 10 ◽  
Renal Tissue ◽  
Protective Role ◽  
Regulatory B Cells ◽  
Tubulointerstitial Injury ◽  
Iri Model

Abstract Background and Aims Acute kidney injury (AKI), even if followed by renal recovery, is a risk factor for the future development of chronic kidney disease (CKD) and end- stage renal disease. It has been postulated that interleukin-10 (IL-10)-producing Regulatory B cells (Breg) play an important role for the tissue repairment in several tissues and organs. Basically, protective role of Breg has been reported in inflammatory bowel disease. In the kidney, it has been shown that IL-10 suppresses renal function decline and improves renal prognosis in IRI model, a typical model of AKI. However, the identity of Breg in the kidney and their origin have not been clarified. Further, how the Breg works during the transition from AKI to CKD is not known. Therefore, first we investigated whether Breg existed in renal tissue on the progression from AKI to CKD in IRI model mice. Further, we performed splenectomy, and examined the renal injury, Breg, and plasma IL-10 levels in this model. Method To examine the existence of Breg in the kidney of IRI model, we used 8-10 weeks-old GFP / IL-10 mice based on C57BL / 6J mice. They are reporter mice for IL-10 producing cells, and can visualize IL-10 producing cells under a fluorescence microscope without fluorescent immunostaining. We prepared following three groups, sham, IRI (unilateral), and IRI + SN (splenectomy) groups. Mice were anesthetized with chloral hydrate (4 g/kg,, intraperitoneal). After making a midline incision, exposed a blood vessel of the left renal pedicles and clamped it for 30 min by clips. one day, 7 days, and 14 days after the surgery, mice were sacrificed, and renal function and plasma IL-10 levels as well as tissue damages by PAS and Masson’s Trichrome staining were assessed. Tissue IL-10-producing cells were detected by flow cytometry. Results There was no difference of plasma IL-10 levels and renal tubulointerstitial injury in IRI group and IRI+SN group on day 1 after IRI. However, on day 7 and day 14, plasma IL-10 levels became gradually higher in IRI group, and SN decreased the increase in IL-10 levels. Tubulointerstitial injury was induced by IRI and SN further worsened tubular damages. Serum Cr and BUN levels were not different in three groups due to normal right kidney. On day 1, number of IL-10-producing B cells increased in the spleen and renal medulla in IRI group confirmed by flow cytometry, which was completely diminished by SN, suggesting that origin of the infiltrated Breg might be spleen, thereby being involved in the protective role in IRI injury in the kidney. Conclusion We report for the first time that Breg might be recruited from spleen by AKI, which may be one of the mechanisms to prevent the progression to CKD.

scholarly journals Lymphocytes are detrimental during the early innate immune response against Listeria monocytogenes

2006 ◽  
Vol 203 (4) ◽  
pp. 933-940 ◽  
Author(s):  
Javier A. Carrero ◽  
Boris Calderon ◽  
Emil R. Unanue
Keyword(s):  
Immune Response ◽  
Listeria Monocytogenes ◽  
Innate Immune Response ◽  
Early Stage ◽  
Bacterial Pathogen ◽  
Interleukin 10 ◽  
Innate Immune ◽  
Type I ◽  
Phagocytic Cells ◽  
Immunodeficient Mice

Mice deficient in lymphocytes are more resistant than normal mice to Listeria monocytogenes infection during the early innate immune response. This paradox remains unresolved: lymphocytes are required for sterilizing immunity, but their presence during the early stage of the infection is not an asset and may even be detrimental. We found that lymphocyte-deficient mice, which showed limited apoptosis in infected organs, were resistant during the first four days of infection but became susceptible when engrafted with lymphocytes. Engraftment with lymphocytes from type I interferon receptor–deficient (IFN-αβR−/−) mice, which had reduced apoptosis, did not confer increased susceptibility to infection, even when the phagocytes were IFN-αβR+/+. The attenuation of innate immunity was due, in part, to the production of the antiinflammatory cytokine interleukin 10 by phagocytic cells after the apoptotic phase of the infection. Thus, immunodeficient mice were more resistant relative to normal mice because the latter went through a stage of lymphocyte apoptosis that was detrimental to the innate immune response. This is an example of a bacterial pathogen creating a cascade of events that leads to a permissive infective niche early during infection.

scholarly journals A protective role of IRF3 and IRF7 signalling downstream TLRs in the development of vein graft disease via type I interferons

2017 ◽  
Vol 282 (6) ◽  
pp. 522-536 ◽  
Author(s):  
K. H. Simons ◽  
H. A. B. Peters ◽  
J. W. Jukema ◽  
M. R. de Vries ◽  
P. H. A. Quax
Keyword(s):  
Vein Graft ◽  
Protective Role ◽  
Type I Interferons ◽  
Type I ◽  
Vein Graft Disease ◽  
Graft Disease

scholarly journals Human cytomegalovirus suppresses type I interferon secretion by plasmacytoid dendritic cells through its interleukin 10 homolog

Virology ◽  
2009 ◽  
Vol 390 (2) ◽  
pp. 330-337 ◽  
Author(s):  
W.L. William Chang ◽  
Peter A. Barry ◽  
Richard Szubin ◽  
Dai Wang ◽  
Nicole Baumgarth
Keyword(s):  
Dendritic Cells ◽  
Human Cytomegalovirus ◽  
Type I Interferon ◽  
Interleukin 10 ◽  
Plasmacytoid Dendritic Cells ◽  
Type I

scholarly journals Multiple Sclerosis Of The Spinal Cord: Is Gadolinium Irreplaceable In Assessing Lesion Activity?

2013 ◽  
Vol 59 (3) ◽  
pp. 158-161
Author(s):  
Constantina Andrada Treabă ◽  
M Buruian ◽  
Rodica Bălașa ◽  
Maria Daniela Podeanu ◽  
I P Simu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Magnetic Resonance ◽  
Contrast Enhancement ◽  
Signs And Symptoms ◽  
Magnetic Resonance Images ◽  
Type I ◽  
Focal Lesions ◽  
Spinal Cord Lesions ◽  
Active Lesion

Abstract Purpose: To evaluate the relationship between the T2 patterns of spinal cord multiple sclerosis lesions and their contrast uptake. Material and method: We retrospectively reviewed the appearance of spinal cord lesions in 29 patients (with relapsing-remitting multiple sclerosis) who had signs and symptoms of myelopathy on neurologic examination and at least one active lesion visualized on magnetic resonance examinations performed between 2004 and 2011. We correlated the T2 patterns of lesions with contrast enhancement and calculated sensitivity and specificity in predicting gadolinium enhancement. Results: Only focal patterns consisting of a lesion’s center homogenously brighter than its periphery on T2-weighed images (type I) correlated significantly with the presence of contrast enhancement (p = 0.004). Sensitivity was 0.307 and specificity 0.929. In contrast, enhancement was not significantly related to uniformly hyperintense T2 focal lesions (type II) or diffuse (type III) pattern defined as poorly delineated areas of multiple small, confluent, subtle hyperintense T2 lesions (p > 0.5 for both). Conclusions: We believe that information about the activity of multiple sclerosis spinal cord lesions in patients with myelopathy may be extracted not only from contrast enhanced, but also from non-enhanced magnetic resonance images.

The protective role of Toll-like receptor 3 and type-I interferons in the pathophysiology of vein graft disease

2018 ◽  
Vol 121 ◽  
pp. 16-24 ◽  
Author(s):  
K.H. Simons ◽  
M.R. de Vries ◽  
H.A.B. Peters ◽  
J.F. Hamming ◽  
J.W. Jukema ◽  
...  
Keyword(s):  
Vein Graft ◽  
Protective Role ◽  
Type I Interferons ◽  
Type I ◽  
Toll Like Receptor ◽  
Vein Graft Disease ◽  
Graft Disease

scholarly journals Interleukin-10 inhibits the osteogenic activity of mouse bone marrow

Blood ◽  
1993 ◽  
Vol 82 (8) ◽  
pp. 2361-2370 ◽  
Author(s):  
P Van Vlasselaer ◽  
B Borremans ◽  
R Van Den Heuvel ◽  
U Van Gorp ◽  
R de Waal Malefyt
Keyword(s):  
Bone Marrow ◽  
Extracellular Matrix ◽  
Osteogenic Differentiation ◽  
Interleukin 10 ◽  
Mouse Bone Marrow ◽  
Type I ◽  
Mrna Levels ◽  
Differentiation Potential ◽  
Alp Activity ◽  
Bone Proteins

Abstract Murine bone marrow cells synthesize bone proteins, including alkaline phosphatase (ALP), collagen type I, and osteocalcin, and form a mineralized extracellular matrix when cultured in the presence of beta- glycerophosphate and vitamin C. Interleukin-10 (IL-10) suppressed the synthesis of these bone proteins and mineralization without affecting cell proliferation. In addition, mRNA levels for the latter proteins were reduced in IL-10-treated cultures. This inhibitory effect was most outspoken when IL-10 was added before ALP activity peaked, eg, day 15 of culture. No significant effect was observed when IL-10 was added at later time points. This finding suggests that IL-10 acts at osteogenic differentiation stages that precede ALP expression but is ineffective on cells that progressed beyond this maturation stage. Likewise, IL-10 appeared to be unable to block both ALP activity and collagen synthesis in the preosteosteoblastic cell lines MN7 and MC3T3 that constitutively synthesize these proteins. Whereas IL-10 did not alter the number of fibroblast colony-forming cells of the marrow, it significantly reduced their osteogenic differentiation potential. In contrast to control cultures, IL-10-treated stroma was unable to either synthesize osteocalcin or to mineralize when subcultured over a 25-day period in the absence of IL-10. The inhibitory activity of IL-10 coincided with significant changes in stroma morphology. Whereas control cultures contained mainly flat adherent polygonal cells, significant numbers of rounded semiadherent to nonadherent cells were observed in the presence of IL-10. Scanning and transmission electron microscopy showed that, in contrast to control cultures, IL-10-treated stromas completely lacked a mineralized extracellular matrix. Collectively, these data suggest that IL-10 may have important regulatory effects on bone biology because of its capacity to downregulate early steps of osteogenic differentiation.

scholarly journals Correlation Between Early Plasma Interleukin 37 Responses With Low Inflammatory Cytokine Levels and Benign Clinical Outcomes in Severe Acute Respiratory Syndrome Coronavirus 2 Infection

2020 ◽  
Author(s):  
Ang Li ◽  
Yun Ling ◽  
Zhigang Song ◽  
Xiaobo Cheng ◽  
Longfei Ding ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Cytokine ◽  
Inflammatory Responses ◽  
Clinical Intervention ◽  
Protective Role ◽  
Interferon Α ◽  
Type I ◽  
C Reactive Protein ◽  
Clinical Prognosis ◽  
Reactive Protein

Abstract Background The immune protective mechanisms during severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection remain to be deciphered for the development of an effective intervention approach. Methods We examined early responses of interleukin 37 (IL-37), a powerful anti-inflammatory cytokine, in 254 SARS-CoV-2–infected patients before any clinical intervention and determined its correlation with clinical prognosis. Results Our results demonstrated that SARS-CoV-2 infection causes elevation of plasma IL-37. Higher early IL-37 responses were correlated with earlier viral RNA negative conversion, chest computed tomographic improvement, and cough relief, consequently resulted in earlier hospital discharge. Further assays showed that higher IL-37 was associated with lower interleukin 6 and interleukin 8 (IL-8) and higher interferon α responses and facilitated biochemical homeostasis. Low IL-37 responses predicted severe clinical prognosis in combination with IL-8 and C-reactive protein. In addition, we observed that IL-37 administration was able to attenuate lung inflammation and alleviate respiratory tissue damage in human angiotensin-converting enzyme 2–transgenic mice infected with SARS-CoV-2. Conclusions Overall, we found that IL-37 plays a protective role by antagonizing inflammatory responses while retaining type I interferon, thereby maintaining the functionalities of vital organs. IL-37, IL-8, and C-reactive protein might be formulated as a precise prediction model for screening severe clinical cases and have good value in clinical practice.

scholarly journals Salivary Melatonin and the Severity of Attachment Loss: A Case-Control Study

2014 ◽  
Vol 2014 ◽  
pp. 1-4
Author(s):  
Leila Golpasand-Hagh ◽  
Faramarz Zakavi ◽  
Arash Daraeighadikolaei ◽  
Akram Ahangarpour ◽  
Sara Hajati ◽  
...  
Keyword(s):  
Chronic Periodontitis ◽  
Healthy Subjects ◽  
Type I Collagen ◽  
Periodontal Diseases ◽  
Protective Role ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Levels ◽  
Melatonin Level ◽  
Type I ◽  
Salivary Melatonin

Background. Melatonin (MT: N-acetyl-5-methoxytryptamine) is a neuroendocrine hormone secreted mainly by the pineal gland in the brain. MT is produced with a circadian rhythm characterized by elevated blood levels during the night. In healthy individuals, maximal secretion of MT occurs between midnight and 2:00 am, whereas the minimal production occurs during the day. MT can be determined by repeated measurement of plasma or salivary MT or urine sulfatoxy-melatonin. Melatonin has powerful antioxidant effects, has an immunomodulatory role, stimulates the synthesis of type I collagen fibers, and promotes bone formation. Melatonin is also secreted in the saliva, although its role in the mouth is not known well. The purpose of this study was to examine the correlation between salivary melatonin level and periodontal diseases. Methods. Fifty subjects by mean age of 40.44±6.38 years were equally divided into 5 groups: 10 healthy subjects, 10 subjects with gingivitis, 10 subjects with localized moderate chronic periodontitis, 10 subjects with generalized moderate chronic periodontitis, and 10 subjects with generalized severe chronic periodontitis. Saliva samples were collected from all the subjects and melatonin levels were determined using an enzyme-linked immunosorbent assay. Two-way and one-way ANOVA and Tukey test were used to analyze relationships among variables. Results. Healthy subjects had significantly higher salivary melatonin level (5.29±0.50 pg/mL) compared to patients with gingivitis (4.35±0.30 pg/mL) (P<0.001). The difference between salivary melatonin level in patients with gingivitis and periodontitis was significant (P<0.001). Level of melatonin in patients with generalized severe chronic periodontitis (3.39±0.10 pg/mL) was significantly lower than that in other groups (P<0.01). Conclusions. This study determined that salivary melatonin level in patients with periodontal diseases is lower than that in healthy subjects. Consequently we conclude that there is a negative correlation between melatonin level and the severity of disease, suggesting that melatonin might have a protective role against periodontal diseases, although further research is required to validate this hypothesis.

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