Review Article
Masutaka Furue; Dugarmaa Ulzii; Yen Vu; Gaku Tsuji; Makiko Kido-Nakahara; Takeshi Nakahara
Abstract
Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction and chronic pruritus. In this review, recent advances in the pathogenesis of AD are summarized. Clinical efficacy of the anti-IL-4 receptor antibody dupilumab implies that type 2 cytokines IL-4 and IL-13 have pivotal roles ...
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Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction and chronic pruritus. In this review, recent advances in the pathogenesis of AD are summarized. Clinical efficacy of the anti-IL-4 receptor antibody dupilumab implies that type 2 cytokines IL-4 and IL-13 have pivotal roles in atopic inflammation. The expression of IL-4 and IL-13 as well as type 2 chemokines such as CCL17, CCL22 and CCL26 is increased in the lesional skin of AD. In addition, IL-4 and IL-13 down-regulate the expression of filaggrin in keratinocytes and exacerbate epidermal barrier dysfunction. Keratinocytes in barrier-disrupted epidermis produce large amounts of thymic stromal lymphopoietin, IL-25 and IL-33, conducing to type 2 immune deviation via OX40L/OX40 signaling. IL-31, produced by type 2 T cells, is a cardinal pruritogenic cytokine. IL-4 and IL-13 also amplify the IL-31-mediated sensory nerve signal. These molecules are particularly important targets for future drug development for AD.
Original Article
Mohsen Arabpour; Atri Ghods; Mahmoud Shariat; Abodl-Rasoul Talei; Fereshteh Mehdipour; Abbas Ghaderi
Abstract
Background: B cells can increase the expression of granzyme B in CD8+ T cells through 4-1BBL/4-1BB interaction and promote anti-tumor immunity. Objective: To investigate the expression of 4-1BBL on B cells in the breast tumor draining lymph nodes (TDLNs) and its association with disease parameters. Methods: ...
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Background: B cells can increase the expression of granzyme B in CD8+ T cells through 4-1BBL/4-1BB interaction and promote anti-tumor immunity. Objective: To investigate the expression of 4-1BBL on B cells in the breast tumor draining lymph nodes (TDLNs) and its association with disease parameters. Methods: Using Ficoll-Hypaque gradient centrifugation, mononuclear cells were isolated from axillary lymph nodes of 42 patients. Cells received 4 hours of PMA/Ionomycin stimulation, in vitro. Both unstimulated and stimulated cells were stained with anti‒CD19 and anti‒4-1BBL antibodies and subjected to flow cytometry. Results: 4-1BBL expression was detected on 2.8 ± 1.7% of unstimulated B cells, while 27.4 ± 11.9% of B cells expressed this co-stimulatory molecule following stimulation. In steady state, the percentage of 4-1BBL+ B cells was not associated with cancer characteristics. However, in patients with invasive ductal carcinoma, the percentage of 4-1BBL expressing B cells in stimulated condition had a decreasing trend in grade III, compared to grade II+I. In addition, significantly higher frequency of 4-1BBL+ B cells was seen in the TDLNs of ER+ or PR+ compared with ER‒ or PR‒ patients (p=0.021 and p=0.015, respectively). No significant associations were observed between the frequency of 4-1BBL+ B cells and the number of involved LNs, Her2 expression or disease stage. Conclusions: The frequency of 4-1BBL+ B cells significantly increased following a short time activation, and showed relative and significant associations with tumor grade and estrogen receptor status, respectively. More investigations are required to evaluate the potential of 4-1BBL+ B cells for use in immunotherapy.
Original Article
Hadi Hossein-Nataj; Mohsen Masjedi; Mohammad Hassan Emami; Mojgan Mokhtari; Fereshteh Alsahebfosoul
Abstract
Background: Increased number of intestinal intraepithelial lymphocytes (IELs) is a key histological finding in the diagnosis of celiac disease (CD); however, the number of IELs in celiac patients and healthy subjects may vary from one region to another. Additionally, there are some seronegative celiac ...
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Background: Increased number of intestinal intraepithelial lymphocytes (IELs) is a key histological finding in the diagnosis of celiac disease (CD); however, the number of IELs in celiac patients and healthy subjects may vary from one region to another. Additionally, there are some seronegative celiac patients with a borderline histology. Objective: To determine the number of the CD3+ and CD8+ IELs T-cells in the celiac patients and healthy subjects (controls) in Isfahan. Methods: The duodenal biopsies were obtained from the celiac patients (n=15) and the controls (n=19). The total number of IELs/100 epithelial cells (ECs) were counted using the hematoxylin-eosin (H&E) staining method, and that of CD3+ and CD8+ IELs/100 ECs were counted using the immunohistochemistry (IHC) staining method. Results: This study defined the upper normal limit for each variable as mean + 2SD. Accordingly, the upper normal limits of the total IELs, CD3+ IELs, and CD8+ IELs/100 ECs were calculated as 37 (95% confidence intervals, CI: 33–41), 22 (95% CI: 19–25) and 12 (95% CI: 10–14), respectively. In 3 clinically CD diagnoses, the total IELs counts/100 ECs were below the upper normal limit, and the histopathological and serologic assays were negative. Nevertheless, the CD8+ IELs T-cells counts/100 ECs showed borderline values. Interestingly, these patients responded to a gluten-free diet (GFD). Conclusions: The study findings suggest that in the clinically diagnosed celiac disease, IELs count/100 ECs below the upper normal limit as well as negative histopathological and serologic assays and the cell density counts of the CD8+ IELs T-cells/100 ECs could be a useful parameter for CD diagnosis and make a decision to put them on a GFD.
Original Article
Lia Farahi; Fatemeh Ghaemimanesh; Saeideh Milani; Seyed Mohsen Razavi; Reza Hadavi; Ali Ahmad Bayat; Ali Salimi; Mohammad Mehdi Akhondi; Hodjattallah Rabbani
Abstract
Background: We have previously reported the aberrant expression of Fibromodulin (FMOD) in patients with chronic lymphocytic leukemia (CLL). Although FMOD has been considered as a cytoplasmic or secretory protein, we discovered the cell surface expression of FMOD in leukemic B cells via anchoring with ...
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Background: We have previously reported the aberrant expression of Fibromodulin (FMOD) in patients with chronic lymphocytic leukemia (CLL). Although FMOD has been considered as a cytoplasmic or secretory protein, we discovered the cell surface expression of FMOD in leukemic B cells via anchoring with glycosylphosphatidylinositol (GPI). Objective: To evaluate FMOD as a new biomarker in CLL patients in comparison with healthy individuals. Methods: A monoclonal antibody was generated against human FMOD. The cell surface expression of FMOD in 52 CLL patients and 45 healthy individuals were compared by flow cytometry. A bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) was used to determine the cell surface localization of FMOD using ELISA and flow cytometry techniques. Annexin V-FITC and propidium iodide (PI) was used to detect apoptosis induction in CLL PBMCs following in vitro incubation with anti-FMOD mAb. Results: The results demonstrated the widespread cell surface expression of GPI-anchored FMOD in CLL patients (median: 79.9 %), although healthy individuals had low FMOD expression (median: 6.2 %) (p≤0.0001). The cut-off value of FMOD expression was estimated with high sensitivity and specificity at 17.9%. Furthermore, in vitro apoptosis induction of leukemic cells following incubation with anti-FMOD mAb showed a direct apoptosis of CLL cells (27.9%) with very low effect on healthy PBMCs (6%). Conclusion: The membrane-anchoring of FMOD by means of a GPI moiety in leukemic cells supports FMOD as a highly potential diagnostic and therapeutic target in CLL patients.
Original Article
Shohreh Fakhari; Hamed Bashiri; Bayazid Ghaderi; Kaveh Tari; Ali Jalili
Abstract
Background: CD93 has originally been known as a C1q receptor, and many studies have demonstrated that CD93 is expressed on hematopoietic stem cells, B cell progenitors, myeloid and monocytic cells. Moreover, CD93 is shown to be expressed on long-lived plasma cells, and CD93 deficient-mice display an ...
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Background: CD93 has originally been known as a C1q receptor, and many studies have demonstrated that CD93 is expressed on hematopoietic stem cells, B cell progenitors, myeloid and monocytic cells. Moreover, CD93 is shown to be expressed on long-lived plasma cells, and CD93 deficient-mice display an impairment in plasma cell development. Objective: To investigate the expression of CD93 on multiple myeloma (MM) cells. Methods: Human MM and B cell lines were cultured, and the expression of CD93 was examined on these cells by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) and Fluorescence Activated Cell Sorting (FACS). In addition, CD19+ primary B cells and CD19-/CD138+ primary MM cells were isolated by MACS columns, and CD93 expression was further analyzed on these cells. Results: qRT-PCR data showed that CD93 expression at mRNA level was much higher in MM cell lines compared with B cell lines. In addition, MM cell lines expressed a higher amount of surface CD93 at protein level compared with B cell lines. More importantly, CD93 expression was significantly higher in CD19-/CD138+ primary MM cells than in CD19+ primary B cells isolated from the bone marrow of patients with MM. Conclusion: We demonstrated that CD93 is expressed on myeloma cells and, that CD93 could play a key role in the pathogenesis of MM. Further studies are necessary to explore this possible role.
Original Article
Majid Tarokh; Marefat Ghaffari Novin; Tahereh Poordast; Zohreh Tavana; Hamid Nazarian; Mohsen Norouzian; Behrouz Gharesi-Fard
Abstract
Background: Endometriosis is a chronic inflammatory disease with the growth of endometrial cells out of uterus and in the peritoneal cavity. T cell subsets participate in the establishment and progress of the disease by producing different cytokines. Objective: To investigate a group of cytokines related ...
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Background: Endometriosis is a chronic inflammatory disease with the growth of endometrial cells out of uterus and in the peritoneal cavity. T cell subsets participate in the establishment and progress of the disease by producing different cytokines. Objective: To investigate a group of cytokines related to Th1/Th2/Th17/Treg subsets within both peripheral blood and peritoneal fluid (PF) samples from infertile endometriosis women. Methods: Peripheral blood and PF samples were collected from 30 infertile endometriosis and 30 non-endometriosis fertile women during laparoscopy. Concentration of cytokines, including TNF-α, IFN-γ, TGF-β1, IL-4, IL-10, IL-17 and IL- 23 were evaluated using ELISA method. Results: Results indicated that the concentration of IFN-γ within serum was significantly reduced in endometriosis group (p=0.001). Regarding PF cytokines, TGF-β1 was increased in endometriosis group (p=0.030). Furthermore, the ratios of IFN-γ/TGF-β1 and IL-17/IL-23 were significantly different between endometriosis and non-endometriosis women in serum samples (pConclusion: Based on the results of the present study, in women with endometriosis, the disturbance of cytokines network might gradually activate the inflammatory responses and tissue repair, resulting in endometriosis development after several years.
Original Article
Nahid Daraei; Mehri Ghafourian; Ata Ghadiri; Afshin Amari; Mahin Najafian; Saber Rokhafrooz
Abstract
Background: The development of a maternal immune response to fetal antigens and deficiency in regulatory T-cells (Tregs) may lead to preeclampsia. A plausible explanation for the reduced Treg cell function in women with preeclampsia is the presence of exhausted Treg cells which express CD279 or programmed ...
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Background: The development of a maternal immune response to fetal antigens and deficiency in regulatory T-cells (Tregs) may lead to preeclampsia. A plausible explanation for the reduced Treg cell function in women with preeclampsia is the presence of exhausted Treg cells which express CD279 or programmed cell death receptor-1 (PD-1), a negative regulatory molecule associated with limited proliferative capacity and reduced immune suppression. Objective: To assess the number of Treg CD4+ CD25high and exhausted Treg CD4+ CD25high CD279+ cells in women with preeclampsia (PE group) and healthy pregnant women (HP group) during the third trimester of pregnancy. Methods: Three-color flow cytometry was used to determine the proportion of Treg and exhausted Treg cells in 40 women in the PE group and 37 women in the HP group. Participants’ blood samples were placed in EDTA blood collection tubes. Peripheral mononuclear cells were separated from the samples and stained with flurochrome-conjugated antibodies against human CD4, CD25 and CD279 markers, and subsequently analyzed by flow cytometry. Results: The PE group had fewer Tregs compared to the HP group (p=0.011). There was a significant increase in the percentage of exhausted PD-1+(CD279) Tregs (p=0.035) in the PE group comparisons with the HP group. Conclusion: The increased number of PD-1 (CD279) molecules on the Treg cells may play a role in preeclampsia, hence it recommendation as a therapeutic target for the disease.
Original Article
Weidong Xu; Zheng Chen; Xiaodong Shen; Chiheng Pi
Abstract
Background: Realgar, an arsenic tetrasulfide compound, is a highly recognized traditional Chinese medicinal prescription that has been widely used to treat various diseases such as inflammatory diseases. However, there are still some problems in the clinical treatment of Realgar, such as large oral dose ...
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Background: Realgar, an arsenic tetrasulfide compound, is a highly recognized traditional Chinese medicinal prescription that has been widely used to treat various diseases such as inflammatory diseases. However, there are still some problems in the clinical treatment of Realgar, such as large oral dose and high potential toxicity. Objective: To evaluate effects of Realgar nanoparticles on lupus nephritis (LN) in vivo in MRL/lpr mice. Methods: Ten-week mice were orally administered every day for eight consecutive weeks except the mice of normal model groups. The serum levels of anti-ds-DNA antibody IgG, IgM, IFN-γ, Creatinine (Cr), and blood urea nitrogen (BUN) were determined, and 24-hour urine protein was also measured. Renal inflammatory pathology analysis was assessed by hematoxylin-eosin (H&E) staining. The expression of phosphorylated signal transducer and activator of transcription 1 (p-STAT 1) and Janus Kinase 1 (JAK 1) in kidney tissue was determined by direct reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Results: The mice treated with Realgar nanoparticle in the high dose-treated (Realgar HD, 0.03 g/kg/d) group exhibited significantly reduced serum levels of anti-dsDNA (p<0.01), IgG (p<0.01), IgM (p<0.01), BUN (p<0.01), Cr (p<0.01), and inflammatory cytokine IFN-γ (p<0.01) as well as proteinuria (p<0.01) compared to the untreated model MRL/lpr mice. Additionally, high doses of Realgar nanoparticles significantly suppressed the phosphorylations of STAT 1 (p<0.01) and the renal pathological changes. Conclusions: The study indicates that Realgar nanoparticles may be a potential agent to treat LN, and the down-regulated p-STAT1 expression suggests that it may be one of the LN treatment targets for Realgar nanoparticles.
Original Article
Ayşe Sağmak Tartar; Şafak Ozer Balın; Ayhan Akbulut; Meltem Yardım; Suleyman Aydın
Abstract
Background:Brucella spp. are facultative intracellular pathogens that can cause chronic infections in many tissues and organs. Objectives: To investigate serum dermcidin, salusin-alpha, salusin-beta and TNF-alpha levels and their correlation with each other in patients with acute brucellosis. Methods: ...
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Background:Brucella spp. are facultative intracellular pathogens that can cause chronic infections in many tissues and organs. Objectives: To investigate serum dermcidin, salusin-alpha, salusin-beta and TNF-alpha levels and their correlation with each other in patients with acute brucellosis. Methods: From 50 patients hospitalized upon diagnosis of acute brucellosis, blood samples were collected and dermcidin, salusin-alpha, salusin-beta and TNF-alpha levels in serum samples were measured using an ELISA assay. The control group included 40 volunteers. Results: Brucellosis group had significantly lower plasma dermcidin, salusin- alpha, salusin-beta levels compared to the healthy control group (respectively p:0.008, p<0.001, p<0.001). Moreover, Brucellosis group had significantly higher plasma TNF-alpha levels comparisons with the controls (p=0.002). In the examination of the correlation between TNF-alpha and dermcidin, salusin-alpha and salusin-beta in the brucellosis group, only a negative correlation was found between salusin-beta and TNF-alpha. In the control group, there was a positive and statistically significant correlation between salusin-beta and TNF-alpha. Conclusion: Dermcidin, salusin-alpha, and, particularly salusin-beta levels are important in Brucella pathogenesis. The paradoxical correlation between TNF-alpha and salusin-beta in patients with brucellosis and control group is remarkable. However, there is a need for extensive studies conducted with more patients to further elucidate this topic.
