To further test the functional attributes of Fab specific for the two-domain RTL1000, we utilized an Fab specific for RTL1000 that was also cross-reactive with a similar U0126 nmr antigenic determinant on RTL342m (α1β1 domains of DR2 linked to mMOG-35-55 peptide). DR2 Tg

mice were immunized with mMOG-35-55 peptide/CFA/pertussis toxin (Ptx) to induce EAE and were treated with pre-formed complexes of 2E4 Fab:RTL342m, the control D2 Fab:RTL342m (specific for RTL2010 that comprised DR4–GAD-555-567 described in Fig. 8C) or TRIS buffer (Fig. 5). As shown in Fig. 5, mice receiving RTL342m plus TRIS buffer were effectively treated, whereas a 2:1 ratio of 2E4 Fab:RTL342m almost completely neutralized the RTL therapeutic effect on EAE. In contrast, a 1:1 ratio of Fab:RTL342m had less neutralizing activity as assessed by daily EAE scores (Fig. 5A) and by the entire experimental effect on EAE for each group as assessed by the cumulative disease index (CDI) (Fig.

5B). Importantly, D2 Fab (also used at a 2:1 ratio) did not neutralize the therapeutic effect of RTL342m on EAE, indicating specificity of the 2E4 Fab for the two-domain RTL342m. In a recent phase I safety study in DR2+ MS subjects 34 to be treated with https://www.selleckchem.com/products/3-methyladenine.html RTL1000 or placebo, we observed detectable baseline plasma levels of two-domain RTL-like structures in 4 of 13 donors (31%). This observation suggested the natural occurrence of two-domain see more structures that could be derived from four-domain intermediates possibly shed from MHC-II expressing APC upon immunization. Using the power of our conformationally sensitive Fabs, we evaluated the appearance and persistence of naturally occurring two-domain MHC-II structures in human MS subjects. Fab 1B11 is specific for the two-domain HLA-DR conformation. It was found to bind to all HLA-DR-derived RTLs (with no peptide specificity), but not to other human and murine allele-derived RTLs or four-domain HLA-DR molecules (Fig. 6A). Serum or plasma samples were diluted 1:10 and adsorbed onto plastic wells pre-coated with the TU39 mAb (that detects all forms of MHC), washed and reacted with 1B11 Fab specific

for HLA-DR-derived RTLs, followed by the addition of enzyme-labeled anti-Fab and substrate for ELISA detection. As shown in Fig. 6B, the 1B11 Fab detected RTL-like material in serum or plasma from the healthy control pool as well as all six MS subjects tested at baseline, with detected levels of protein ranging from 13 to 1100 ng/mL. These results indicate for the first time the existence of soluble serum MHC-II structures with a distinct RTL-like conformation that differs from the classical membrane-bound MHC conformation. Increased signal for two-domain MHC-II was also observed in subject ♯42 after 30 min of infusion of 200 mg RTL1000 and in subject ♯44 after 2 h of infusion of 100 mg RTL1000, consistent with increased levels of injected RTL1000.

We then tested each subject’s vaccine response for enrichment of gene sets from the same database collection as used before using ssGSEA and identified the gene sets most differentially enriched in

the high responders compared with the low responders. We found 13 gene sets significantly associated with a high HAI response to vaccine (FDR < 0.25) (Fig. 2A). The number of gene sets and degree of enrichment of gene sets correlated with TIV antibody response was lower than what we observed in the comparison of pre- and post-YF-17D vaccination. This suggests that the biological “signal” associated with influenza vaccine response is less pronounced than the effect of click here vaccination with YF-17D. The gene sets that were enriched in responders were from a wide array of studies and sources (Supporting Information Table 2) and the genes in most gene sets were nonredundant (Supporting Information Fig. 2), suggesting that the gene sets represented diverse biological processes. However, using a constellation www.selleckchem.com/products/BIRB-796-(Doramapimod).html plot, we found two distinct but connected clusters of gene sets (Fig. 2B). We used DAVID annotation as a tool to provide secondary annotation for the two clusters

of genes and found that one cluster (indicated by the orange arc) was strongly enriched for immunoglobulin and complement genes. The second cluster (indicated by the purple arc) was strongly enriched for genes associated with proliferation (Supporting Information Table 3). Only a subset of proliferation-related gene sets contained in MSigDB enriched in responders (Supporting Information Fig. 3) suggesting that the proliferation signature present in vaccine responders is not shared by all tissue types. Alternatively, other proliferation-related gene sets in the compendium may also entrain other biological responses not present in vaccine responder expression profiles. We reasoned that if these clusters of highly connected gene sets enriched in samples from vaccine responders represented bona fide biological processes, then

the genes shared by each of these clusters should be overrepresented for physically interacting genes. To test this, we projected the genes Urease found in the gene set clusters into InWeb [18] a curated protein–protein interaction network (PPI; Fig. 2C and D). We found that there was a high degree of physical connectivity between the component genes of the antibody gene cluster (p = 10−3), and between the genes in the proliferation cluster (p = 10−2) (Fig. 2C and D). This suggests that the clusters of enriched gene sets found in responders represented coordinated upregulation of genes in functional networks. We confirmed these findings using a second, independent source of gene sets, described by Chaussabel et al.

As CMV-specific cells were endowed with features of effector CTL, freshly purified CMVPent+ CTL were directly co-cultured with HLA-A2-expressing T2 cells loaded with control

or CMVpp65495–503 peptide (CMV peptide), in the presence or absence of IFN-α. IFN-α enhanced the production of IFN-γ, but did not affect the surface expression of CD107a (Fig. 7A). Accordingly, IFN-α did not alter the immediate lytic activity of CMV-specific AZD9291 chemical structure CTL (Supporting Information Fig. 7D). Current adoptive therapies developed to treat CMV infection after allogenic bone marrow transplantation involve isolation of circulating CMV-specific CD8+ T cells from healthy donors, in vitro expansion and infusion into the patients 17. To explore how IFN-α could affect the process of in vitro expansion, sorted CMVPent+ cells were cultured for 4–5 days with IL-2-conditioned medium alone or together with IFN-α2b, Beads or Beads in combination with IFN-α2b

or IFN-α5. IL-2 was absolutely necessary for proliferation and survival of isolated CMV-specific cells (Supporting Information selleck products Fig. 7E). As shown by the CFSE dilution profiles of CMVPent+ cells from five individuals, cells underwent division in a synchronized manner regardless of the starting differentiation stage of sorted cells (Fig. 7B and Supporting Information Fig. 7F–G). CMV-specific cells in the presence of IL-2 divided without CD3/CD28-stimulation (Supporting Information Fig. 7F), indicating that the CMVpent used for the sorting sufficiently signaled through TCR/CD3. Overstimulation with Beads retarded proliferation of CMVpent-triggered cells (Supporting Information Fig. 7F). IFN-α slightly delayed the division driven by CMVpent-mediated TCR engagement either alone (Supporting Information Fig. 7G) or together with CD3/CD28-triggering (Fig. 7B). The cell expansion upon stimulation with CMVpent and Beads was clearly lowered by IFN-α (Fig. 7C). In the presence of IL-2, CMVpent-triggered

Avelestat (AZD9668) cells secreted IFN-γ (Supporting Information Fig. 7H), and the levels of secreted IFN-γ increased if the cells were further stimulated with Beads. Addition of IFN-α enhanced the amounts of IFN-γ secreted (Fig. 7D and Supporting Information Fig. 7H). Next, we examined the IFN-α effects on the effector functions of the expanded CMV-specific cells. Hence, CMV-specific CTL cultured for 4–5 days with Beads+IL-2 in the presence or absence of IFN-α were deprived overnight of IL-2 and subsequently co-cultured with T2 target cells loaded with control or CMV peptide. Figure 7E shows that cells expanded in the presence of IFN-α produced higher amounts of IFN-γ and mobilized more efficiently CD107a to the surface than cells expanded without IFN-α. Similarly, there was a minor but significant enhancement of the cytolytic activity against peptide-loaded targets (Fig. 7F and G). Both IFN-α subtypes tested showed similar behavior (Fig. 7).

This might reflect a complicated and paradoxical GSK-3β regulation system toward apoptosis in different cell states. Alternative apoptotic signalling other than GSK-3β-dependent apoptosis presumably occurs in quiescent conditions whereas GSK-3β-dependent apoptosis emerges upon the extracellular stimulation. Translocation of β-catenin, resulting from GSK-3β activation, was believed to be involved in the impaired cell proliferation by activation of TLR4.38 Here we provide an alternative explanation

for the impaired cell survival by TLR4. β-Arrestin 2 not only terminates G-protein couple receptor signalling but also regulates other signalling selleck compound pathways.18β-Arrestin 2 signalling complex with Akt/GSK-3β has been well established by Beaulieu et al.,30,31 which illustrates the activation of GSK-3β by β-arrestin 2 through scaffolding PP2A to Akt.30 Conversely, β-arrestin 2 suppresses GSK-3β activity through stabilization

of pGSK-3β in the SD-induced apoptotic paradigm in the present study. The different regulation in specific physiological conditions may account for such discrepancy. Moreover, β-arrestin 2 is required for serum-dependent cell survival, just like the PI3K pathway, both of which converge on the inactivation of GSK-3β. It is currently uncertain how β-arrestin 2 stabilizes pGSK-3β, despite the confocal images supporting the effective co-localization of GSK-3β with β-arrestin 2 (data not shown) and our unpublished data suggest that β-arrestin 2 advances GSK-3β phosphorylation in the presence of LPS. However, our data Fulvestrant in vitro strongly indicate that β-arrestin-2-mediated inactivation of GSK-3β prevents SD-induced apoptosis. Apparently, over-activation of GSK-3β leads to the failure of inhibited apoptosis by β-arrestin 2. The egradation of β-arrestin 2 in HEK293/TLR4 is possibly responsible for the amplification of the GSK-3β-dependent apoptotic cascade. Hence, apart from the well-defined effects on NF-κB1, IκBα, TRAF6 and GRK5 Aprepitant in the TLR4 cascade,18,19,39 GSK-3β is expected to be the additional potent effecter of β-arrestin 2 in the TLR4-primed

apoptotic cascade. Generally, β-arrestin 2 mediates signalling regulation through directly binding to the respective signalling molecules. It gives rise to the question of whether β-arrestin 2 scaffolds with GSK-3β, and subsequently a complex is formed to serve as a molecular switch for activation of proliferative or apoptotic pathways. We have tried but failed to resolve the problem by searching for the putative interaction between β-arrestin 2 and GSK-3β by co-immunoprecipitation, but the correlated study is well underway. However, β-arrestin 2 association of GSK-3β is strongly considered in a growing list of signal patterns that modulate the induction of apoptosis by TLR4. The mechanism by which SD influences the TLR4 signalling pathway is unclear.

“
“Calciprotein AT9283 ic50 particles (CPP) are a novel marker of mineral stress. High levels of CPP are found in patients with calciphylaxis, a condition associated with marked vascular calcification and a poor prognosis. We report substantial reductions in CPP levels in a dialysis patient having combined haemodialysis (HD) and plasma exchange (PEx) prior to an ABO-incompatible kidney transplant. We also report the effects of the same treatments combined with sodium thiosulphate (STS) in a patient newly diagnosed with calciphylaxis. Combining HD with intra-dialytic STS and PEx we achieved a significant reduction in CCP with the least

rebound between treatment sessions. After 6 weeks of treatment, the CPP reduction was paralleled by clinical improvement. Measurement of CPP may be an attractive marker for monitoring the effectiveness of calciphylaxis therapy. “
“The usefulness of the absolute N-terminal pro-brain natriuretic peptide (NT-ProBNP) concentration and its digit number for screening for cardiac disease was explored in new haemodialysis patients.

A cross-sectional study involving 71 (68 ± 14 years, 83% male) new dialysis patients was conducted. Receiver operator characteristic curve analysis was performed to identify the cutoff level of NT-proBNP for identifying cardiac disease at https://www.selleckchem.com/Wnt.html the start of dialysis. The median NT-proBNP concentration was 6576 pg/mL just before the first dialysis session and its mean digit number was 4.3 ± 0.6. Overall, 67%, 52%, 9% and 35% of patients had left ventricular (LV) hypertrophy, LV dilatation, systolic dysfunction and significant coronary artery disease, respectively. NT-proBNP levels of about 6000, 10 000 and 14 000 pg/mL were the best cutoff levels for the diagnosis of coronary artery disease (AUC, 0.754; P < 0.001), LV systolic dysfunction (area under the curve (AUC), 0.765, P = 0.001) and Org 27569 LV dilatation (AUC, 0.685, P = 0.008), respectively. Interestingly, 4.5 was the best digit number cutoff for all cardiac abnormalities. These findings suggest that a digit number of 5 or more means a potentially

high risk for cardiovascular disease and a digit number of 3 or less means a relatively low risk. The NT-proBNP concentration just before the first dialysis session is a useful tool for screening for cardiac abnormalities. Considering the wide variation of the NT-proBNP cutoff levels depending on each cardiac abnormality, the digit number could be potentially easier to use for initial risk stratification for cardiac disease in new dialysis patients. “
“Angiotensin receptor antagonists (ARBs) and anti-oxidants reduce urinary protein excretion and delay progression of immunoglobulin A (IgA) nephropathy. We investigated the efficacy and safety of probucol (an anti-oxidant) combined with valsartan (an ARB) on the progression of IgA nephropathy.

, 2009). They suggested that hspMaori is a marker for the entire Austronesian expansions rather than only for Polynesians and their findings point to Taiwan as the source of the Austronesian expansions. They determined that hspMaori was widespread among aboriginal Taiwanese tribes and their phylogenetic analysis also showed that the genetic diversity was significantly higher in Taiwanese hspMaori than in non-Taiwanese

hspMaori. The non-Taiwanese hspMaori haplotypes formed selleck chemical a single clade, the Pacific clade, which originates from one of several clades among indigenous Taiwanese haplotypes. Polynesians, Melanesians, and Filipinos were included in this Pacific clade. This might explain the presence of East Asian type H. pylori strains in Philippines; however, the majority of CagA type was Western type. It is possible that the intermarriages of the various races and

nationalities with the indigenous ethnic groups and the strong Western influence and culture in the Philippines have resulted in more Western-type H. pylori strains in the country. hpEurope is common in Europe and countries colonized by Europeans (Yamaoka et al., 2008). The Philippines was a former colony of Spain (333 years), and it has also extensive relations and communications with Western countries. Compared with other East or Southeast Asian Sirolimus price countries, the incidence of gastric cancer in the Philippines is quite low. This may be a reflection of the mostly Western CagA type of Philippine H. pylori strains; however, gastric cancer is a multifactorial disease (Hatakeyama, 2009) and incidence cannot be solely attributed to the type of bacteria or bacterial virulence factor. Investigations on a greater number of H. pylori strains isolated

from Philippine patients need to be carried out. In conclusion, the present study found that Cepharanthine cagA is present all H. pylori strains examined from the Philippines. Philippine populations are considered to originate from Austronesian expansions; however, the major type of CagA in the Philippines is the Western type. These findings support that the modern Western influence has resulted in more Western-type H. pylori strains in the Philippines, which may explain the low incidence of gastric cancer, and H. pylori-infected Filipinos can be considered to be at a low risk of developing gastric cancer. In addition, J-Western strains are unique in Okinawa and different from other Western CagA-positive strains in Asian countries such as the Philippines, Thailand, and Vietnam. We thank Ms Kumiko Sueyoshi for her technical assistance. This work was partly supported by funds from the Japan Society for the Promotion of Science. “
“This review article summarizes current knowledge on regulation, functions, and capacities of stem cells in the female and male reproductive tract.

Methods: Vesical pressure measurement

during the continuous infusion of the urinary bladder with saline, acetic acid (AA, 0.1%) or IWR1 prostaglandin E2 (PGE2, 10−5 M) were performed in un-anesthetized rats. Multi-unit recording from bladder afferent nerves preformed under urethane anesthesia. Laser irradiation, either continuously at 1 W or in 10 W-pulse mode, was delivered at 830 nm from 1.5 cm above the skin at the lumbosacral joint. Results: During continuous saline infusion to the urinary bladder, neither continuous (1 W) nor pulse (10 W) laser irradiation altered the intercontraction interval and nerve firing during distention of the bladder. Pulse laser, but not continuous laser irradiation, increased the intercontraction interval with AA or PGE2 infusion and diminished nerve firing during distention

of the bladder with AA or PGE2 infusion. Conclusion: These data indicate that pulse laser could diminish inflammation related nerve firing from the bladder. Since this laser irradiation did not affect the normal bladder distention elicited nerve firing, it appears capable of reducing urgency sensation without loss of the basic micturition reflex. “
“Objectives: To compare the effectiveness and safety of solifenacin versus propiverine in the treatment of overactive bladder (OAB), in a single-blind, randomized parallel study. Methods: Sixty-six patients with OAB (14 men and 52 ABT-263 nmr women) were randomly assigned to groups: solifenacin (5 mg/day) or propiverine (20 mg/day) and treated selleckchem for 8 weeks. The primary outcome variable

was mean change from baseline to end of treatment in urgency of the OAB symptom score (OABSS). Secondary outcomes were bladder diary variables: change over 24 h in the mean number of voids (daytime and nighttime), episodes of micturition urgency and incontinence, and mean volume voided. Patients also completed total OABSS and the King’s Health questionnaires. Results: Group backgrounds were comparable except for the male to female proportion; 11:22 for solifenacin (n = 33) versus 3:30 for propiverine (n = 33). Adverse events were 6 of 29 (21%) for solifenacin versus 14 of 26 (54%) for propiverine (P = 0.017). Three patients were withdrawn for voiding difficulty (one in solifenacin and two in propiverine) and one patient for dry mouth (propiverine group). Change in OABSS urgency score was −2.3 ± 1.4 for solifenacin (n = 28) versus −1.3 ± 1.7 for propiverine (n = 23), (P = 0.0169). Total OABSS and other individual scores, and voiding diary parameters for both drugs showed improvements; however, between-group difference was not established. Conclusion: Although both solifenacin 5 mg and propiverine 20 mg were effective in the treatment of OAB, solifenacin appeared to be more effective and tolerable.

In contrast,

pharmacodynamic (PD) monitoring examines the physiological effects of a drug rather than using the surrogate marker of drug concentration. Combining PD with PK monitoring has the potential to improve therapeutic drug dosing, thereby increasing efficacy and safety in an individual patient. The purpose of this review is to provide the clinician with an overview of the recent literature on the methodology and use of immune function Ganetespib monitoring in the field of kidney transplantation. Both B and T lymphocytes have been implicated in the pathogenesis of acute and chronic allograft rejection. However, perhaps because T cells are the major targets of most immunosuppressant drugs, and B-cell effector mechanisms depend on T-cell help, T-cell biology has received significantly greater attention as a potential PD marker (Table 1, Fig. 1). T-cell assays can be broadly divided into two major categories: donor antigen specific or non-antigen specific.

Donor antigen specific assays involve stimulation of immune cells ex vivo with donor-derived mitogen such as donor lymphocytes. Non-antigen specific assays can be antigen independent CDK inhibitor (e.g. measurement of lymphocyte subsets), or assess the functional state of T cells following stimulation with a polyclonal stimulant (e.g. phytohaemagglutinin (PHA), concanavalin A, phorbol 12-myristate 13-acetate/ionomcyin and pokeweed mitogen). Although donor-derived stimuli may be more specific in determining immune reactivity to the allograft, the limited availability of donor cells precludes repeat testing in the clinical setting. As such, polygenic stimuli are more likely to be applied in routine clinical practice. Only non-antigen specific assays will be discussed further in this review. Additionally, detailed discussion of the techniques for each of these assays is beyond the scope of this paper (for this, see review by Najafian et al.36). Fluorescent-activated cell sorting (FACS) analysis is a simple and sensitive method that allows sorting and quantification of lymphocyte

subsets by fluorescent labelling of cell surface markers. Although a number of studies5,6 have shown mafosfamide that standard triple immunosuppressive regimens lead to significant reductions in the CD4+/CD8+ ratio in transplant recipients without effecting total lymphocyte number,5,6 there are only very limited and conflicting data linking lymphocyte subset counts with clinical outcomes. Although one study reported that decreased CD4 helper activity was associated with a lower risk of rejection, there was no relationship between the actual pre-transplant T or B-cell subset counts and acute rejection or 1-year graft function. However, the same study did show a correlation between elevated pre-transplant CD8+ suppressor-effector T-cell subset counts (CD8+CD11b+) and the occurrence of post-transplant infection.

No wound complications occurred in any patient. Functional and aesthetic outcomes were satisfactory in all patients. This flap design is effective for reconstructing large skin defects of the upper back. © 2013 Wiley Periodicals, Inc. Microsurgery 34:20–22, 2014. Closing large skin defects of the upper back is a challenging problem.[1] Transfer of a pedicled latissimus dorsi musculocutaneous flap is the method of choice for reconstruction in this region[2]; however, primary closure of the donor site can interfere with closure Epacadostat in vitro of the recipient site, which can become enlarged depending on the

orientation of the skin island. A simple solution is combined use of a skin graft; however, wound healing problems and significant contour deformities can develop.[3, 4] To reconstruct large skin defects of the upper back, we have developed an efficient design for a latissimus dorsi musculocutaneous flap that does not require skin grafts. We describe our surgical technique and report the outcomes of four cases. From March 2011 to September 2012,

we used pedicled latissimus dorsi musculocutaneous flaps to repair large skin defects of the upper back immediately after wide excision of malignant tumors in four consecutive patients, and Z-VAD-FMK purchase these patients were included in this study. Defects with a minor diameter greater than 10 cm were defined as large defects. Two patients were men and two were women, and their mean age was 51.5 years. Our design concept was based on the principle that the shape of the skin defect being reconstructed is changed when primary closure of the adjacent flap donor site is attempted.[5] We took advantage of this principle and developed a flap with a donor site whose primary closure changes the shape of the skin defect being reconstructed from circular to elliptical and, therefore, makes it easier to reconstruct. The operative procedure was usually performed with the patient Thiamine-diphosphate kinase in either the lateral or the prone position. After tumor ablation, the line of least skin

tension at the defect was determined with a pinch test. The ipsilateral latissimus dorsi musculocutaneous flap was designed so that the longitudinal axis of its skin island was perpendicular to this line (Fig. 1, left). We pinched the flap donor site to simulate primary closure and confirmed that the shape of the recipient site will change from circular to elliptical (Fig. 1, center). Then, the defect was partially closed at either end or both ends, and the required flap size was determined by reference to the remaining defect. Finally, an elliptical skin island was designed on the latissimus dorsi muscle along the axis mentioned above. The flap was raised in the regular manner and transferred to the defect through a subcutaneous tunnel. The amount of the latissimus dorsi muscle included in the flap depended on the dead space of the defect.

In-vitro differentiative potential of MSCs is not restricted

to mesodermal lineages, but their transdifferentiation into other lineages, such as endothelia, could be realized Doxorubicin both in vitro and in vivo [5]. In addition, MSCs exhibit immunoregulatory activities, inhibiting the function of different immune cells of innate and adaptive immunity [6], blocking the division of stimulated T cells, preventing irreversible G0/G1 phase arrest and stopping T cell division in mixed lymphocyte reactions (MLRs) [7]. However, the immunomodulatory activity of the MSCs does not rely solely upon T cells, but also upon the first step of the immune response through the inhibition of dendritic cell differentiation and maturation in antigen-presenting cells [8]. Furthermore, their regulatory activity may be amplified by modulating immune responses via the de-novo induction and expansion of CD4+CD25+forkhead box protein 3 (FoxP3)+ regulatory T cells (Tregs). Tregs play a critical role in peripheral self-tolerance, as well as in the regulation of acquired immunity, by inhibition of lymphocyte proliferation [9, 10]. As well as Tregs developing in the

thymus (natural Tregs), a Treg population can be induced from peripheral naive STA-9090 purchase T cell (inducible Tregs), and these inducible Tregs can be recruited directly by MSC from CD4+ T cells [11, 12]. In recent decades many studies have been published addressing the role of Treg number and function in human autoimmunity [13], suggesting that their possible defective function plays a role in many autoimmune diseases. On this basis, both the regenerative and the immunomodulatory properties of MSCs make them an attractive candidate Thalidomide for cellular therapy in autoimmune diseases. Systemic sclerosis (SSc) is an autoimmune disease in which alteration of cellular immunity, including T and B lymphocytes, has been largely

studied both in the skin and in internal organs [14, 15]. Furthermore, recent evidence has shown an aberrant dendritic cell function in SSc, contributing to the molecular milieu of the disease [16]. We have shown previously that MSCs obtained from SSc patients (SSc–MSC) were normal with respect to clonogenicity and differentiative capacity, although they displayed early senescence and were defective in acquiring some differentiative functions [17]. Senescent MSC generally show a flattened morphology, over-expression of senescence-associated β-galactosidase (β-Gal) activity, reduced telomerase activity and increased expression of both p53 and p21, which are negative regulators of cell proliferation [18]. At present, only few papers have investigated the immunoregulatory activity in SSc.