The total median BVAS/WG score in these patients was 5 (IQR 3–8), and median BVAS/WG score calculated for eye and airway involvement was 3 (2.8–5.5) (Fig. 1). The frequency of disease distribution and BVAS/WG scores are shown in Table S2. At 6 months, a significant decrease was HM781-36B manufacturer observed in BVAS ENT-EYE-L score [medians before 3 (3–6) versus 2 (1–3), P = 0.02]. Five patients (29%) had a ≥50% treatment response regarding the ENT-EYE-L

manifestations including 1 patient with complete remission. Ophthalmic manifestations, confirmed by MRT in three patients, improved clinically in two patients and progressed in one patient. No clinical improvement was seen in three patients with endobronchial disease in response to RTX treatment (Fig. 4). One patient with tracheal-subglottic stenosis improved clinically, whereas no treatment response was seen in the second learn more patient and progression was observed in the third patient. Multiple nodules and cavities in the lungs diagnosed in five patients resolved in four cases within 5–8 months after RTX treatment initiation, and in one patient, a significant improvement was seen (Fig. 5). For more detailed descriptions, see Supporting information. Rituximab was generally well tolerated, and no serious infusion reactions were observed. No deaths occurred during the follow-up period. However, eight patients (28%)

experienced severe life-threatening events or required hospitalization during the follow-up period because of severe infections. Two patients (7%) needed additional medications owing to pulmonary Pneumocystis jiroveci infections, and one had a severe Aspergillus pneumonia infection. One patient had a severe Herpes infection with Adenosine triphosphate signs of meningitis that was successfully treated with acyclovir. Three patients (10%) developed severe neutropenia, whereas one of them displayed generalized bone marrow suppression. Although these three patients received high doses

of oral CYC also, the additive effect of RTX should be considered. During the follow-up period, one patient was diagnosed as having breast cancer. Another patient with a severe relapsing disease (duration more than 27 years) and multiorgan involvement was hospitalized three times during follow-up period owing to erysipelas, sepsis and septic arthritis. This patient had previously been diagnosed as having a urinary bladder cancer 3 years before RTX treatment. One patient suffered haemorrhagic cystitis, a common complication of CYC treatment. The current standard therapy for ANCA-associated vasculitis is high-dose steroids and CYC, the latter being associated with severe adverse events such as leucopoenia, cancers, severe infections, gonadal failure and premature menopause in women. Although it is effective in approximately 80% of patients [17], there is an unmet need for more efficient and less toxic therapies in these patients.

As the eosinophilic structure (appearing pale pink) surrounding condensed Purkinje cell bodies (appearing dark

pink) was reminiscent of the halo in Lewy bodies, we named this peculiar change as, “halo-like amorphous materials”. Following our report of this peculiar Purkinje cell change, nearly 10 patients have been so far reported to show similar morphological changes in Purkinje cells.6 All the patients in who genetic tests for 16q-ADCA were performed harbored the same single-nucleotide C-to-T (−16 C > T) change in the puratrophin-1 gene specific to 16q-ADCA.7 learn more Therefore, making the diagnosis of 16q-ADCA among numbers of cerebellar degenerations seemed to become feasible based on this neuropathologic hallmark, “halo-like amorphous materials”. We next studied the halo-like amorphous materials immunohistologically

to clarify what are the components of this peculiar change.4,5 First, we studied the cytosolic calcium binding protein calbindin D28k, which is expressed exclusively in Purkinje cells in the cerebellum. On immunohistochemistry for calbindin D28k, we observed various morphological changes of Purkinje cells. For example, numerous somatic sprouts selleck chemical stemming from a Purkinje cell body was occasionally seen (Fig. 3a). In such cases, a zone with calbindin D28k immunoreactivity appeared corresponding to the halo-like amorphous materials. On other occasions, calbindin D28k immunoreactive “granules” were found outside Purkinje cells (Fig. 3b,c). Sometimes, calbindin D28k immunoreactive puncta appeared to create a zone surrounding the Purkinje cell body, suggesting that remnants of somatic sprouts constitute at least a part of halo-like

amorphous materials (Fig. 3b). Calbindin D28k-positive granules were also found distant from the Purkinje cells even though the halo-like amorphous materials themselves did not show obvious immunoreactivity against calbindin D28k (Fig. 3d). From these observations, we considered that the somatic sprouts from Purkinje cells are among the important constituents of the halo-like amorphous materials. We next studied synaptic proteins since Purkinje cells are known to receive synaptic inputs from various types of neurons. For this purpose we studied synaptophysin, OSBPL9 one of the pre-synaptic vesicle proteins. The numbers of synaptophysin-immunoreactive granules attaching to Purkinje cell bodies were not increased in SCA6 brains used as controls. On the other hand, such granules were remarkably increased in number in 16q-ADCA, creating a zone of synaptophysin-immunoractive structures surrounding Purkinje cell bodies (Fig. 4a). Such increased zones sometimes even extended up to the primary shaft of the Purkinje cell dendrites (Fig. 4b). This clearly added increased presynaptic terminals, conceivably originating from neurons other than Purkinje cells, as an important component of halo-like amorphous materials.

A battery of 36 vaginal isolates of C. glabrata was tested against PSC and FLC to determine their in vitro susceptibilities. The 48-h geometric mean MICs for all isolates tested were 0.156 and 4.238 μg ml−1 for PSC and FLC respectively. Two strains of C. glabrata for which FLC MICs were different were selected for in vivo study. The treatment regimens for the vaginal murine infection model were PSC or FLC at 10 or 20 mg kg−1 of body weight/day and 20 mg kg−1 twice a day. Regimens with PSC at 20 mg kg−1 once or twice a day were effective in reducing the load of both the FLC-susceptible and -resistant isolates of C. glabrata. FLC

at 20 mg kg−1 twice a day was effective in reducing the PLX4032 load of both the isolates of C. glabrata. PSC displayed a more effective in vivo activity than FLC in the treatment of murine C. glabrata vaginitis. “
“The bis-coumarin daphnoretin and its monomeric precursors scopoletin and umbelliferone were isolated for the first time from the aerial part of Loeselia mexicana Brand (a vegetal species used in Mexican traditional medicine)

using chromatographic Fulvestrant manufacturer techniques. The structures of these compounds were determined by 1H and 13C NMR analyses. These coumarins were evaluated for in vitro antifungal activity. The three compounds tested showed significant antifungal activity. “
“Recurrent candidaemia is both a cause and a symptom of deep organ candidiasis or infection of foreign bodies (e.g. central venous line, other indwelling catheter or pacemaker wire) and is associated with significant morbidity and mortality. This case report demonstrates that in the event of pacemaker Thymidylate synthase wire infection with Candida and when it is not possible to remove the infected pacemaker wire, treatment with an echinocandin, such as anidulafungin, can be safe and successful. “
“Scedosporium apiospermum is a ubiquitous filamentous fungus that may infect immunocompetent patients after trauma and may cause severe and often fatal infections in immunocompromised hosts. Here, we present the case of a 28-year-old female with S. apiospermum

infection on the left forearm that had developed while she was on long-term immunosuppressant therapy. Analysis of a skin biopsy specimen showed a mixed cell granuloma with hyaline septate hyphae. Culture of the abscess revealed S. apiospermum which was identified as S. apiospermum sensu stricto by sequencing of the internal transcribed spacer-1 region of ribosomal DNA genes. Resection of the eruption and oral itraconazole (100 mg day−1) therapy for 4 months was effective in curing the infection. “
“Sporotrichosis is a subacute or chronic fungal infection caused by Sporothrix schenckii, which is commonly acquired by traumatic inoculation of the fungus carried in a contaminated material into the skin. Joint involvement is the most frequent extracutaneous manifestation in immunosuppressed patients. We report the case of an immunocompetent woman who acquired sporotrichosis through the scratch of a sick cat.

Genetically, neither of the patients had any mutation in the TDP-43 gene. In conclusion, we consider that although PLS may be a clinically significant disease entity, at autopsy, the majority of such clinical cases would present as upper-motor-predominant amyotrophic lateral sclerosis with FTLD-TDP. “
“Viral spread

during the early stages after infection was compared between a highly neurovirulent mouse hepatitis virus (MHV), JHMV cl-2 strain (cl-2), and its low-virulent mutant, soluble-receptor-resistant (srr)7. The infection of cells with srr7 Sorafenib (soluble-receptor-resistant mutant 7) is dependent on a known MHV receptor (MHVR), carcinoembryonic cell adhesion molecule 1a, whereas cl-2 shows MHVR-independent infection. Initial viral antigens were detected between 12 and 24 h post-inoculation (p.i) in the infiltrating

cells that appeared in the subarachnoidal space of mouse brains infected with viruses. There were no significant differences in the intensity or spread of viral antigens in the inflammatory cells between the two viruses. However, 48 h after infection with cl-2, viral antigen-positive cells in the grey matter with the shape of neurons, which do not express MHVR, were detected, while srr7 infection was observed primarily in the white matter. Some of the viral antigen-positive inflammatory cells found in the subarachnoidal space during the early phase of infection reacted with anti-F4/80 or anti-CD11b monoclonal antibodies. Syncytial giant cells (SGCs) expressing viral and CD11b antigens were also detected among these inflammatory cells. These antigen-positive PI3K inhibitor cells appeared in the subarachnoidal space prior to

viral antigen spread into Edoxaban the brain parenchyma, indicating that viral encephalitis starts with the infection of infiltrating monocytes which express MHVR. Furthermore, the observation indicates that viral infection has cytopathic effects on the monocyte lineage, which plays a critical role in innate immunity, leading to the rapid spread of viruses during the early stage of infection. “
“Contiguous ABCD1 DXS1357E deletion syndrome (CADDS) is a contiguous deletion syndrome involving the ABCD1 and DXS1357E/BAP31 genes on Xq28. Although ABCD1 is responsible for X-linked adrenoleukodystrophy (X-ALD), its phenotype differs from that of CADDS, which manifests with many features of Zellweger syndrome (ZS), including severe growth and developmental retardation, liver dysfunction, cholestasis and early infantile death. We report here the fourth case of CADDS, in which a boy had dysmorphic features, including a flat orbital edge, hypoplastic nose, micrognathia, inguinal hernia, micropenis, cryptorchidism and club feet, all of which are shared by ZS. The patient achieved no developmental milestones and died of pneumonia at 8 months. Biochemical studies demonstrated abnormal metabolism of very long chain fatty acids, which was higher than that seen in X-ALD.

In the next subsections, we will illustrate the protective effects mediated by Ab–FcR interactions in the context of a selection of infections with intracellular bacteria and parasites. Legionella pneumophila are Gram-negative bacteria that, when inhaled, can infect and replicate within alveolar macrophages and cause a severe form of pneumonia known as Legionnaire’s disease. Upon contact with the macrophage, L. pneumophila uses its Icm/Dot type IV secretion system (T4SS)

to inject a large number of effector proteins into the cytosol of the selleck screening library host cell 63. This promotes phagocytosis and modulates trafficking within the host cell, resulting in the evasion of phagolysosomal fusion and the establishment of a replication-permissive vacuole 64. We have recently shown that this Icm/Dot T4SS-mediated subversion of trafficking within the host cell does not take place in the presence of specific Abs as, in such circumstances, L. pneumophila is targeted to lysosomes and can no longer replicate intracellularly 65. Thus, opsonized L. pneumophila are targeted click here into

degradative pathways, indicating that specific Abs can effectively oppose the events initiated by the T4SS. The opsonization of L. pneumophila with specific Abs does not interfere with the function of the T4SS itself but it is actually the cross-linking of activating FcRs on the surface of macrophages that renders these host cells nonpermissive for intracellular replication of L. pneumophila. The importance of FcR triggering for this protective effect was demonstrated both in vitro and in vivo; however, the lysosomal targeting of L. pneumophila is not simply a direct consequence of FcR-mediated endocytosis and subsequent phagolysosomal fusion since macrophages, which had received an FcR trigger before infection with nonopsonized bacteria, also effectively targeted L. pneumophila to lysosomal compartments and hence did not permit

their intracellular replication 65. These Thymidine kinase results suggest that FcR cross-linking induces a signaling cascade that effectively counteracts the modulation of host cell trafficking by Legionella effectors and redirects the bacteria to lysosomes where they are degraded. By arresting phagosome maturation M. tuberculosis survives and replicates in membrane-bound compartments in macrophages 66. Ab responses have long been believed to play a negligible or even detrimental role in protection against this intracellular bacterium, whereas cell-mediated immunity was assigned to be crucial in resolving infections. Nevertheless, newer findings implicate a role for Abs in protection against mycobacterial infections 67, 68. mAbs of the IgG3 or IgG1 subclass recognizing surface Ags of M. tuberculosis such as the carbohydrate lipoarabinomannan (LAM) have been shown to prolong survival of intratracheally or intravenously M.

There were 635 accepted abstracts, and a total of 145 oral presentations. In addition Acalabrutinib research buy to all this immunology, the meeting had a vibrant social program (as discussed below). The registration fee of the main conference was kept affordably low, taking into account the difficult economic situation in which all of us currently live and the cuts that have hit the research community in recent years. Fortunately, the meeting received crucial support from 7 silver and 17 bronze sponsors (http://www.immunology2011.it/sponsor.asp),

7 minor sponsors, 6 pharmaceutical companies for the clinical symposia and the cooperation of 2 media operations, including the European Journal of Immunology. As a teaser, just before the opening ceremony, the opening symposium entertained the fascinating new developments in microscopy that allow cells of the immune system to be tracked in vivo, capturing the dynamics of cellular movements and interactions. While M. Gunzer (Magdeburg/Essen) observed neutrophils at work, M. Iannacone (Milano) followed lymphocytes in a viral infection. How microscopy can be used to identify and track individual molecules was discussed by M. Reth (Freiburg), who provided evidence for an oligomeric see more resting state of the B-cell antigen receptor and the perturbation

of this state by activation. The opening ceremony started with the two national anthems followed by a concert given by a duo Phenylethanolamine N-methyltransferase from Modena: the Butterflies. Francesca Bergamini, vocals, and Alessandra Fogliani at

the piano, performed songs in German, Italian, Spanish and English (Fig. 1). The first keynote lecture of the meeting was sponsored by EFIS and given by Prof. Klaus Rajewsky (Boston, USA). He presented his in-depth analysis of B-cell activation and the role of c-myc and IKK in the pathogenic transformation for the survival and expansion of lymphoma cells. At the end of the opening ceremony, the President of the DGfI, Prof. Dieter Kabelitz (Kiel), awarded Prof. Hans-Hartmut Peter (Freiburg) honorary membership of the DGfI for his extraordinary impact on clinical immunology and rheumatology, and his contributions to the understanding of immunodeficiencies. After the opening session, high up on the PalaRiccione terrace with its impressive view of the sea bathed in a beautifully colored sunshine, a famous brass band from Münster (the NorthWestBrass, led by Kapellmeister Roland Göhde, Fig. 2) had the opportunity to present a new poly-functional program – from J. S. Bach to Bob Dylan, passing through Gershwin, Henry Mancini, The Beatles, Abba – to more than 600 persons who were also interested in testing the speed of evaporation of 350 bottles of ice-cold Prosecco (from Travani A. et al., Arzene, Italy, a total of 262.

Total proteins from Mtb subcellular fractions (10 or 50 μg per lane) were subjected to SDS-PAGE (Invitrogen, USA) and transferred to a nitrocellulose membrane. The membrane was blocked with 5% non-fat milk in tris-buffered saline containing 0.1% Tween high throughput screening compounds 20 (TBS-T) and probed with the monoclonal supernatant (Clone 276.B7/IgG1κ) or anti-19 KD lipoprotein mAb (clone IT-19; kindly provided by Dr. Antônio Rothfuchs, NIH/NIAID-TVTRM Contract) at 1:1000 dilution followed by incubation with HRP-conjugated secondary Ab (1:2000). Detection was

performed by ECL analysis (Pierce, USA). Thirty-four patients with active pulmonary TB in the Division of Respiratory Diseases of the Central Public Health Clinic of Juiz de Fora, Minas Gerais State and 11 active-diseased patients from Hospital Octávio Mangabeira, Bahia, Brazil were selected. Only those patients with detectable AFB in the sputum bacilloscopy or culture-confirmed disease and who had INCB024360 molecular weight undergone clinical and chest X-ray examinations, as prescribed by the Brazilian Ministry of Health, were included in the study. AIDS, diabetes, hepatitis, hypertension, pregnancy, and alcoholism were exclusion

criteria. All patients included in the study have been confirmed to present negative bacilloscopy following treatment. Thirty-eight healthy BCG-vaccinated, which constituted the endemic control (EC) group formed by medical students and staff from UFJF, five foreign PPD-negative non-BCG-vaccinated subjects (the non-endemic group) and six PPD-negative BCG-vaccinated individuals were included in the control groups without prior history of Mtb infection. All patients and control

subjects have been informed of the study and have given consent for blood sampling. The UFJF Medical Ethics as well as the Oswaldo Cruz Foundation Committees have approved the study protocols (UFJF-1495.186.2008; CPqGM-219 (CAAE) 2221.0.000.225-06). Histological sections from pleural TB patients or control leprosy patients were deparaffinized in xylene, rehydrated in alcohol and water. Quenching of endogenous peroxidase was performed with a 1.5% hydrogen peroxide-methanol solution for 20 min. Sections were incubated next with normal goat serum (30 min 37°C) and then exposed to monoclonal anti-sMTL-13 supernatant (Clone 276.B7). Incubations with biotinylated goat anti-mouse Ab with streptavidin−HRP complex (Vectastain Elite ABC reagent, Vector Laboratories, CA, USA) were performed for 30 min at 37°C. Positive reactions was detected with 3,3′-diaminobenzidine (Dako Cytomation, CA, USA), followed by Harris’s hematoxylin counterstaining. Sections were examined microscopically and images were acquired using a Sight DS-5M-L1 digital camera (Nikon, Melville, NY, USA) connected to an Eclipse 50i light microscope (Nikon). Maxsorb plates (Nunc, Denmark) were coated with rec-sMTL-13 in carbonate buffer overnight at 4°C. Plates were washed with PBS/0.05% Tween-20.

When mice treated with 22D1 mAb were inoculated i.p. with HK-C. albicans, oxidative burst by rpMϕ was significantly reduced (Fig. 4D middle and right panels), demonstrating that SIGNR1 plays a role in oxidative burst Selleck Silmitasertib at least in rpMϕ. To confirm the interaction of SIGNR1 with Dectin-1 in rpMϕ, we stained the cells with specific Ab before and after the addition of HK- or live C. albicans. Co-localization of SIGNR1 and Dectin-1 was very limited without microbes, but their accumulation at the contact site with HK- and live microbes

on phagosomal membrane was observed (Fig. 5A). Physical association of these two molecules was also detected only when rpMϕ were stimulated (Fig. 5B), and such an association was shown to

be induced rapidly (Fig. 5C). To explore the role of SIGNR1 in C. albicans recognition, we prepared sSIGNR1 and sDectin-1 tetramers, instead of the previously formed Dectin1-Ig-fusion proteins 9, 24. Thermal treatment of sSIGNR1 with Strep-Tactin at 37°C enhanced binding activity. This result may be due to the aggregation of SIGNR1 via its long neck domain (116 amino acids), which contains a heptad-repeat sequence, leading to increased ligand affinity and specificity, as previously reported 22, 25. Our study and several other reports indicate that Dectin-1 and TLR2 MLN8237 recognize microbial components and induce inflammatory responses in either a cooperative 15, 29, 30 or independent manner 13, 14. In RAW-control cells, zymosan induced weak oxidative burst, but TLR ligand-depleted zymosan and PAM3CSK4 did not. By contrast, TLR ligand-depleted zymosan induced a significant

oxidative burst in RAW-SIGNR1 cells, and this response was not enhanced by PAM3CSK4. In addition, TLR2 blocking mAb had no effect on their oxidative burst in RAW-SIGNR1 cells. Based on these results, TLR2 is not largely involved in the oxidative burst response. SIGNR1 was shown to enhance the intracellular oxidative burst of rpMϕ in response to HK-C. albicans. Such an enhancement was due to the recognition of microbes via CRD, since RAW-SIGNR1 cells lacking CRD function were unable to elevate the response. In addition, binding/capture of microbes by SIGNR1 was demonstrated to be crucial for the enhanced oxidative response by the experiment titrating the number of microbes Calpain during the culture. Dectin-1-specific inhibitors, such as laminarin and anti-Dectin-1 mAb, blocked the oxidative response in RAW-control cells, whereas these reagents by themselves showed no effect on the response in RAW-SIGNR1 cells. However, they were able to inhibit the response in cooperation with reagents to SIGNR1, as previously reported in the case of zymosan binding in rpMϕ 23. In addition, piceatannol, a Syk-specific inhibitor, totally blocked the response in not only the RAW-control but also RAW-SIGNR1 cells, demonstrating that the SIGNR1-dependent enhanced response relies on the Syk-mediated signaling pathway.

Although comparisons of phenotypic activities among these variants have been attempted, there are few detailed reports on this. In this study, we examined typical EPEC strains isolated from diarrheal and healthy persons for polymorphism of the bfpA and perA genes, presence or absence buy BGJ398 of BFP-related genes, and such virulence-associated characteristics as autoaggregation, adherence to HEp-2 cells and contact hemolysis. The nucleotide primer sets eaek1/eaek4 and bfpAks/bfpAkcomas were used for PCR to amplify and identify eae and bfpA genes, respectively (Table 1). A total of 53 typical EPEC strains (eae+ bfpA+) isolated in Japan (27 strains) and Thailand (26 strains) from healthy humans and patients with

diarrhea, and 2 reference EPEC strains, E2348/69 (O127a: H6) (17) and 886L (O111: H2), were used in this study. In addition, the KI1924 and KI1455 strains, neither of which has the eae nor bfpA gene, were used as negative controls. The O and H serotypes were determined with antisera kits (Denka-Seiken, Tokyo, Japan) and H8-antisera (Statens Serum Institut, Copenhagen, Denmark). Detection of eae and BFP-related genes (bfpA, bfpF, perA, GSK1120212 datasheet perC, and pchA) was performed

by PCR using specific primers for amplification. The specific primers used in this study are shown in Table 1. The DNA template was prepared by suspension of a bacterial culture grown overnight on an antibiotic medium 3 agar plate (Difco, BD, Sparks, MD, USA) with 100 μl of distilled water, followed by boiling for 10 min. PCR assays were performed Wilson disease protein in 25 μl of a reaction mixture consisting of PCR buffer (20 mM Tris-HCl pH 8.4, 50 mM KCl, and 1.5 mM MgCl2), 0.1 mM dNTPs, 0.1 μM of each primer, 1 unit/0.2 μl of Taq polymerase (Promega Corporation, Madison, WI, USA) and 2 μl of template DNA. The reactions were run in a DNA thermal cycler 9600 (Roche Molecular Biochemicals, Indianapolis, IN, USA) for 25 cycles of denaturation (94 C for 30 sec), annealing (50 C or 55 C for 1 min), and extension (72 C for

1.5 min), with a final extension at 72 C for 10 min. PCR products were electrophoresed on a 13% polyacrylamide gel electrophoresis system and visualized with ethidium bromide under ultraviolet light. The typing of eae and bfpA was performed by HMA as previously described (34, 35). HMA is a convenient way of determining the similarity of sequences from their heteroduplex mobility in polyacrylamide gel electrophoresis (36). Amplicons obtained from the bfpA-PCR and perA-PCR were subjected to HMA. An appropriate amount of amplicons was mixed with 2 μl of the amplicons from a reference strain, 2 μl of 50 mM EDTA [pH 8.0], and sterile distilled water added to 10 μl. The mixture was denatured at 94 C for 5 min, re-annealed at 72 C for 3 min and at 50 C for 1 hr. The heteroduplexes were electrophoresed on a 10% polyacrylamide gel, containing 5% stacking gel, in Tris-glycine buffer without SDS.

Natural Tregs (nTregs) develop in the thymus whereas induced regulatory T cells (iTregs) differentiate

in peripheral sites.1In vitro differentiation of iTregs is mediated by T-cell receptor (TCR) -mediated activation together with transforming growth factor-β (TGF-β) and interleukin-2 (IL-2).2 Both types of Tregs constitutively express Foxp3 [forkhead (FKH)-winged helix family protein of transcription regulators], which is the master gene mediating the immunosuppressive function of Tregs.3,4 It is likely that the induction of Foxp3 expression in Tregs Doramapimod research buy with TGF-β is secondary to activation of the enhancer and promoter regions of the Foxp3 gene, as well as being secondary to regulation of histone

acetylation and DNA demethylation of the Foxp3 gene.5,6 The role of TGF-β in Treg induction in vivo is unclear because the optimal concentrations of TGF-β used to induce Foxp3 expression in vitro are unlikely to be present in vivo. Statins are widely used drugs for the treatment of hypercholesterolaemia. They function as competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), which is the rate-determining enzyme of the mevalonate pathway. More recent studies have also suggested that statins can mediate immunosuppressive functions and have proven effective in the treatment of autoimmune diseases or graft-versus-host disease in animal models.7–9 A number of mechanisms have been proposed to explain the immunosuppressive effects of the statins including inhibition of antigen presentation by inhibition of the induction of MHC class II expression, check details and blocking of T helper type 1 (Th1) cell differentiation by inhibiting

TCR-specific phosphorylation of Stat4 in Th1 differentiation.7,10 Suppression of Th1 differentiation Montelukast Sodium by statins in the experimental autoimmune encephalomyelitis mouse model was mediated by inhibition of protein geranylgeranylation, one of the main downstream metabolic branches of the mevalonate pathway.10 Statins may also interfere with the interaction between T cells and antigen-presenting cells by inhibiting the functions of the β-integrin, lymphocyte function-associated antigen 1 (CD11a/CD18).11 Although direct effects of statins on Treg function have not been reported, a number of studies have suggested that Tregs play an important role in the control of pathology in atherosclerosis and atherosclerotic plaques have been reported to contain a lower percentage of Foxp3+ Tregs compared with normal tissue.12,13 Recently, a study has reported that the number of Foxp3+ T cells is elevated in the peripheral blood mononuclear cellsof patients who take statins.14 However, it is still unclear if statins directly increase the number of Foxp3+ cells or indirectly modulate the trafficking of Tregs into blood or to sites of immunopathology.