The exact composition of tolerosomes is not known, but it is thought that they may contain other co-stimulatory molecules, which may induce tolerance to the MHC-associated peptide (42). The discovery of tolerosomes is relatively recent, having occurred less than 10 years ago. It has been known since 1983 that, in order for oral tolerance to develop, an intact portal circulation

is needed, and that oral tolerance is transferrable through serum. These cell fragments, the so-called tolerosomes, first discovered by electron microscopy in 2001, were found in the insoluble fraction produced by ultracentrifugation from the serum of animals which had been subjected to induction of oral tolerance. The soluble fraction, serum without tolerosomes, was no longer able to mediate the transfer of oral tolerance (41). This proved that intercellular communication occurs through exosomes

during development HDAC inhibitor of oral tolerance. The fate of tolerosomes after their production has not yet DAPT manufacturer been fully elucidated. It is supposed that they bind to local or distant antigen presenting cells (43, 44), conveying the necessary information for mounting tolerance to food antigens. In any case, the fact that the portal circulation is involved in this process has lead to the speculation that tolerosomes can be directed to the liver, another recognized tolerogenic site (45, 46). Oral tolerance

has been exploited for therapeutic purposes to inhibit all forms of unwanted immune responses, from the secretion of different antibody classes, to type IV hypersensitivity reactions. It is to be noted that Th1-type responses are much easier to inhibit than Th2 responses. In order to suppress a Th2 immune response, it is necessary to administer greater antigen quantities, or to increase the frequency of administration (47). An exception to this rule is that of IgE-mediated Th2 immune responses associated with increased production of IL-4, such as allergies, Reverse transcriptase which respond very well to oral tolerization schemes (48). The idea of using SEA in order to augment oral tolerance to different peptides arose from epidemiologic studies (49). Staphylococcus aureus is now a common commensal in the gut in the occidental population (50, 51). It has been demonstrated that Western infants with a greater degree of colonization with SEA-producing S. aureus strains are protected against food allergy (52, 53). Toxigenic S. aureus residing in the gut induce greater concentrations of IgA in children’s serum and protect from eczema (54). Animal models of allergic diseases suggest that neonatal oral administration of SEA followed by feeding the sensitizing protein OVA in adulthood prevents the development of airway allergy when the mice are re-exposed to intranasal OVA (35).

The laboratory of O. Neyrolles is supported by the Centre National de la Recherche Scientifique, the Fondation pour la Recherche Médicale

(FRM), the Agence Nationale de la Recherche, the European Union, and the Fondation Mérieux. G. Lugo-Villarino holds a fellowship from FRM. The funders had no role in the decision to publish this article or in its preparation. The authors declare no financial or commercial conflict of interest. “
“Insulin-dependent (type 1) diabetes is a prototypic organ-specific autoimmune disease resulting from the selective destruction of insulin-secreting β cells within pancreatic islets of Langerhans by an immune-mediated inflammation involving autoreactive CD4+ and CD8+ T lymphocytes which infiltrate pancreatic islets. Current treatment is substitutive, i.e. chronic use of exogenous insulin which, in spite of significant advances, is still associated with major constraints selleck inhibitor (multiple daily injections, risks of hypoglycaemia) and lack of effectiveness over the long term in preventing severe degenerative complications. Finding a cure for autoimmune diabetes by establishing effective immune-based therapies is a real medical health challenge, as the disease incidence increases steadily in industrialized countries. As the disease affects mainly children and young adults, any candidate immune therapy must therefore be safe and

avoid a sustained depression of immune responses with the attendant problems of recurrent infection and drug Rapamycin toxicity. Thus, inducing or restoring immune tolerance to target autoantigens, controlling the pathogenic response while preserving the host reactivity to exogenous/unrelated antigens, appears to be the ideal approach. Our objective is to review the major progress accomplished over the last 20 years towards that aim. In addition, we would like to present another interesting possibility to access new preventive strategies cAMP based on the ‘hygiene hypothesis’, which proposes a causal link between the increasing incidence

of autoimmune diseases, including diabetes, and the decrease of the infectious burden. The underlying rationale is to identify microbial-derived compounds mediating the protective activity of infections which could be developed therapeutically. Identifying insulin-dependent or type 1 diabetes (T1D) as a polygenic autoimmune inflammatory disease is a relatively recent finding which occurred by the end of the 1970s. The academic diabetes community reacted rapidly to this important discovery, concentrating efforts to approach, first, the major issue of the early diagnosis of the immunological disease and secondly, to devise immune-based therapeutic strategies to delay and/or prevent disease progression. Compared to other autoimmune diseases, approaching the pathophysiology of T1D was problematic because of the difficulties in having direct access to the target organ in patients.

However, low doses were as efficient and induced prolonged suppression. It is possible that this prolonged suppression was due to Treg cells, which might be eliminated with high doses of chimeric A9H12 but not, or to a lesser extent, with low doses. That anti-LAG-3 antibodies

can eliminate Treg cells was demonstrated previously in a transplantation model, where very high doses could prevent tolerance induction and even break an established tolerance [15]. The DTH response has been well characterized in immunized animals, including rhesus monkeys [27,28], and humans as an antigen-specific reaction resulting in erythema and induration (within 24–72 h) at the site of injection. It is characterized as a type IV hypersensitivity Doxorubicin molecular weight reaction involving cell-mediated Pirfenidone concentration immunity initiated by CD4 and CD8 T cells. The exposure to Mycobacterium tuberculosis that we used here drives a cytokine-induced differentiation of naive CD4 Th cells to Th1 [29], and therefore can be considered as a surrogate in vivo assay for psoriasis inflammation. In conclusion, we demonstrated that selectively targeting activated T cells with a LAG-3 cytotoxic antibody prevents T cell-driven skin inflammation in a preclinical DTH model in non-human primates. Our data suggest that depleting

pathogen-specific activated LAG-3+ T cells might represent a promising new therapeutic approach in diseases where self-antigens (or alloantigens in the case of transplantation) and activated T cells (e.g. multiple sclerosis, rheumatoid arthritis, psoriasis, different forms of thyroiditis,

diabetes type I) are involved. This work was supported in part by the ‘Progreffe’ foundation, by a grant from the Agence Nationale pour la Recherche no. ANR-06-RIB-010–01 and by a research grant from Immutep SA. The authors thank R. Bredoux for assistance in project new management and C. Mary and A. Cariot for advice in pharmacokinetic evaluation. T. H., F. T. and B. V. are inventors of the WO2008132601(A1) patent application on anti-LAG-3 antibodies. “
“Susceptibility to Chlamydia trachomatis infection is increased by oral contraceptives and modulated by sex hormones. We therefore sought to determine the effects of female sex hormones on the innate immune response to C. trachomatis infection. ECC-1 endometrial cells, pre-treated with oestradiol or progesterone, were infected with C. trachomatis and the host transcriptome analysed by Illumina Sentrix HumanRef-8 microarray. Primary endocervical epithelial cells, prepared at either the proliferative or secretory phase of the menstrual cycle, were infected with C. trachomatis and cytokine gene expression determined by quantitative RT-PCR analysis. Chlamydia trachomatis yield from progesterone-primed ECC-1 cells was significantly reduced compared with oestradiol-treated cells.

The organization of these gVLR genes differs depending on the gene and species (2b). The possible combinations of VLRA and VLRB are estimated to generate a potential repertoire that is almost equivalent to the TCRs

and BCRs of jawed vertebrates, (> 1014) [22]. This observation suggests that VLRs are the antigen receptors of jawless vertebrates. Consistent with this, lampreys immunized with human erythrocytes or anthrax spores of Bacillus anthracis produce antigen-specific soluble VLRB molecules that act as antibodies [22], [23]. These observations indicate that, despite their lack of structural similarity to the HSP inhibitor review antigen receptors of jawed vertebrates, VLRs function as antigen receptors in jawless vertebrates. During development of LLCs, LRR modules are inserted into the gVLR gene by a gene conversion-like

mechanism (2c) [19], [24]. Multiple LRRNT-, LRR1-, LRRV-, LRRVe-, CP- and LRRCT-encoding modules are located proximally to the gVLR gene. A homologous sequence is used to prime the insertion of those modules during VLR assembly. The sequences located at the ends of the most newly copied LRR module determine the next LRR module. In this way, LRR modules are unidirectionally inserted into the gVLR gene. Although, monoallelic assembly of the VLRA and VLRB genes occurs in the majority of cases, diallelic assembly has MG 132 been observed in a few cases [25]. In such instances, one mature VLR gene encodes a functional VLR structure, while the other does not. The

unsuccessful mature VLR gene contains an in-frame stop codon. These observations indicate that an inhibitory feedback mechanism regulates VLR assembly. The molecular mechanism of VLR assembly is still unknown. However, two CDAs, CDA1 and CDA2, have been identified as candidate molecules that may mediate gene conversion [19]. Generation of antibody diversity by gene conversion in birds, rabbits and cattle requires AID, which belongs to the apolipoprotein B mRNA editing enzyme, catalytic Bcl-w polypeptide family of molecules [26]. Phylogenetic analysis and secondary structure prediction suggest that AID and CDA1 are more closely related to each other than are AID and CDA2. Over-expression of the CDA1 molecule in yeast confers a mutagenic phenotype and increases the rate of intragenic recombination. Previous reports have revealed that CDA1 and CDA2 are expressed in VLRA+ and VLRB+ LLCs, respectively [27]. Thus, the jawless vertebrate CDA1 and CDA2 molecules may control gene conversion-like processes in VLRA+ and VLRB+ LLCs, respectively. Jawless vertebrates possess both soluble and membrane-bound forms of VLRB [17], [28]. Soluble VLRB antibodies are organized into pentamers or tetramers of dimers, similarly to immunoglobulin M of jawed vertebrates. The cysteine residues that are located in the 3′-invariant stalk region are required for VLRB antibodies to form oligomers.

Importantly, investigation of the cellular immune dysregulation showed that macrophages, not uNK cells, were activated to produce TNF-α and infiltrate the placental zone.35 Taken together, these results demonstrate that in response to certain pathogens,

IL-10 is a protective agent. Furthermore, the absence of IL-10 allows investigation of the pathogenesis of bacterial and viral motifs at sub-clinical click here levels. On the other hand, as a simple rule of nature, IL-10 cannot be presented as a global suppressive agent against all infectious agents. Our recent results are intriguing in that IL-10 does not protect pregnancy against mimics which represent double stranded RNA viruses (unpublished observations). T regulatory (Tregs) cells in the decidua have recently come under the microscope of pregnancy research. Their characteristic ability to produce suppressive cytokines in response to foreign antigen makes Tregs promising therapeutic targets for intervention toward adverse pregnancy outcomes. Tregs are characterized as CD4+/CD25+/Foxp3+, and their ability to produce IL-10 is well documented.36 The presence of Tregs was assessed in the murine decidua. Unpublished data from our laboratory and others show that murine Tregs appear in the estrous cycle and increase early in pregnancy, peaking on gd10–12 and declining thereafter.37,38 Spontaneous fetal resorption in abortion prone CBA×DBA/2

mice can be abrogated by adoptive transfer of Tregs harvested from same gestational age WT mice. Importantly, neutralization of IL-10 in the aforementioned experimental setting abolishes the ability of WT Tregs to rescue CBA×DBA/2 fetal resorption.39 much Birinapant Finally, recent observations in humans have shown that decidual Tregs can inhibit immune stimulation of conventional T cells through cell-cell contact or IL-10 production.40 Recent findings

suggest that uterine Tregs may be of peripheral blood origin and their development toward the uterine phenotype may be under hormonal control.41 Migration studies with human decidual Tregs show that Tregs migrate to areas of hCG production. Women with ectopic pregnancies or spontaneous abortion show decreased IL-10 production coupled to low levels of Treg migration to trophoblast/hCG+ dense regions.42 Interestingly, murine CD4+/CD25− cells treated with E2 were converted to Foxp3+ T cells that produced IL-10, lending further evidence that Tregs may be under hormonal control.43 However, one study posits that decidual Treg development may be driven in part by the presence of paternal antigen as pseudopregnant females (mated with vasectomized males) showed increased levels of decidual Tregs.44 Unpublished data from our laboratory show that Treg numbers do not differ between WT and IL-10 null pregnancies over the spectrum of gestation. However, we have begun to address differences in functionality of Tregs from IL-10−/− versus WT mice.

In this manuscript, we review some of the most prominent

characteristics of inwardly remodeled resistance arteries including their changes in vascular passive diameter, wall thickness, and elastic properties. Then, we explore the known contribution of the different components of the vascular BGB324 wall to the characteristics of inwardly remodeled vessels, and pay particular attention to the role the vascular smooth muscle actin cytoskeleton may play on the initial stages of the remodeling process. We end by proposing potential ways by which many of the factors and mechanisms known to participate in the inward remodeling process may be associated with cytoskeletal modifications and participate in reducing the passive diameter of resistance vessels. “
“The spectrum of the laser Doppler signal contains information on speed distribution of particles moving in the volume interrogated by the photons traveling from the source to the detector. The measured laser Doppler spectrum represents superposition of spectra formed by distribution of Doppler frequency shifts scaled along the frequency

axis for different speeds of the moving particles. The method of spectrum decomposition was validated in phantom experiments and by assessment of speed distributions of red blood cells moving in microvascular network during venous and arterial occlusion as well as during thermal stimulation. “
“Lymphatic filariasis, one of the most debilitating diseases associated with the lymphatic system, affects over Selleck PLX3397 Pyruvate dehydrogenase a hundred million people worldwide and manifests itself in a variety of severe clinical pathologies. The filarial parasites specifically target the lymphatics and impair lymph flow, which is critical for the normal functions of the lymphatic system in maintenance of body fluid balance and physiological interstitial fluid transport. The resultant contractile dysfunction of the lymphatics causes fluid accumulation and lymphedema, one of the major pathologies associated with filarial infection. In this

review, we take a closer look at the contractile mechanisms of the lymphatics, its altered functions, and remodeling during an inflammatory state and how it relates to the severe pathogenesis underlying a filarial infection. We further elaborate on the complex host–parasite interactions, and molecular mechanisms contributing to the disease pathogenesis. The overall emphasis is on elucidating some of the emerging concepts and new directions that aim to harness the process of lymphangiogenesis or enhance contractility in a dysfunctional lymphatics, thereby restoring the fluid imbalance and mitigating the pathological conditions of lymphatic filariasis. “
“HIV-1 infection of the CNS is associated with impairment of CBF and neurocognitive function, and accelerated signs of aging.

Our study is the first to evaluate the percentage of blood monocytes in CRPS patients. Although the percentage of total monocytes Forskolin manufacturer (CD14+ peripheral blood mononuclear cells) remained unchanged in CRPS, the percentage of the CD14+CD16+ monocyte subgroup was elevated significantly (P < 0·01) in individuals afflicted with CRPS compared to healthy controls. Previous studies have

determined that these cells represent a potent antigen-presenting and proinflammatory subpopulation of monocytes [28] that has been shown to be expanded in inflammatory conditions [34]. Although there was no correlation between the increased number of CD14+CD16+ monocytes in the CRPS group and the patients’ overall pain level, there was a correlation between increased numbers of CD14+CD16+ monocytes in CRPS patients demonstrating cold allodynia. This finding

suggests that the increased percentage of CD14+CD16+ monocytes may be associated with central sensitization. As reported previously, there was no difference in plasma levels of TNF-α, IL-10, IL-8, IL-6 and IL-1β between CRPS patients and controls [35,36]. However, individuals with high levels of CD14+CD16+ monocytes demonstrated a significantly Buparlisib lower (P < 0·05) plasma level of IL-10 compared to individuals with low levels of CD14+CD16+. This is consistent with a study showing that CD14+CD16+ monocytes produce similar levels of the proinflammatory cytokines TNF-α, IL-6 and IL-1β and lower levels of the anti-inflammatory cytokine IL-10 [26]. This study also showed that the percentage of lymphocytes (T helper cells, T cytotoxic cells, NK cells or B cells) did not differ between CRPS patients and healthy control individuals. These results are in agreement with the study of Ribbers and colleagues that reported no association between lymphocyte subpopulations and patients with reflex sympathetic dystrophy (currently referred to as CRPS-type 1) [37]. A subsequent study by Kaufmann and colleagues also found no changes in the percentage of T cytotoxic cells, NK cells and B cells in CRPS patients [38]. However, they reported a reduction

of T helper cells (CD8+ lymphocytes) as well as an increase in the CD4/CD8 ratio [38] in CRPS patients compared to healthy controls. Although our study also 5-FU concentration found a small reduction of CD8+ lymphocytes and an increase in the CD4/CD8 ratio, these changes were not statistically significant (P > 0·05). The elevation in the percentage of CD14+CD16+ monocytes seen in CRPS patients in this study could be due to the syndrome itself or may result from other factors. Factors such as physical inactivity, morbid obesity and sleep have been shown to alter the percentage of CD14+CD16+ monocytes [39–41]. Morbidly obese individuals have been reported to show elevated levels of the CD14+CD16+ monocyte subset [39]. The percentage of obese individuals (BMI > 30) in both the CRPS and control groups was approximately 20%.

1), B220 (clone RA3-6B2). Intracellular AIRE staining was performed using the BD Cytofix/Cytoperm kit according to the manufacturer’s instructions 9. Cell sorting and analysis were performed on FACS (DakoCytomation MoFlo®, DakoCytomation MoFlo® XDP, BD FACSAria™, BD FACSCanto™, BD FACSCalibur™). Normal and transduced cells were plated on chamber slides (ICN Biomedicals) and permeabilised using the BD Cytofix/Cytoperm™ Fixation/Permeabilization Kit. For AIRE staining, cells were incubated with monoclonal rat anti-AIRE Ab (Clone 5H12) Napabucasin followed by Alexa

568 nm goat anti-rat IgG (H+L) (Invitrogen). For the detection of MOG protein, cells were stained with monoclonal mouse anti-MOG Ab (Clone 8-18C5; gift from Prof. C Bernard, MISCL, Monash University, Victoria, Australia) followed by secondary Ab (Alexa 594 nm goat anti-mouse IgG). Slides were mounted using Dako Fluorescence mounting medium (Dako Cytomation) and images acquired with an Olympus IX71 Inverted Research Microscope. For confocal microscopy, transduced cells were cultured on glass coverslips, fixed with 4% PFA in PBS and permeabilised with 1% Triton X-100 in PBS prior to staining. Cells were stained with FITC-conjugated

anti-AIRE 5H12 9 and nuclear stain Hoechst 33342 (Sigma), mounted using fluorescent mounting media (Dako) and images acquired on a confocal microscope (Leica TCS SP2, Leica Microsystems). Statistical significance was evaluated using two-tailed Student’s t test for 2 groups. p values less than or equal to 0.05 were considered significant (*p≤0.05, find more **p≤0.01, ***p≤0.001). Significant difference between two curves was evaluated via a permutation test offered by the Walter and Eliza Hall Institute for Medical Research (Melbourne, Australia) (http://bioinf.wehi.edu.au). We thank K. Webster for help with mTEC isolation and

P. Crewther for animal and laboratory management. We thank AMREP and WEHI Animal Services for animal care and management. This work was supported by fellowships from La Fondation pour la Recherche Medicale (FRM) and the (-)-p-Bromotetramisole Oxalate 6th FP of the EU, Marie Curie, contract 040998 (to F.-X.H.), by Australian Postgraduate Awards (to S. A. K), NHMRC fellowships (171601 and 461204), NHMRC program grants (257501, 264573, 406700), Eurothymaide and EURAPS, 6th FP of the EU, and the Nossal Leadership Award from the Walter & Eliza Hall Institute of Medical Research to H. S. S., and NHMRC project grant (491004), to F. A., H. S. S. and F. X. H. Conflict of interest: The authors declare no financial or commercial conflict of interest. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. “
“This unit describes methods for isolating mouse monocytes and neutrophils, as well as in vitro protocols for measuring cell migration and polarization.

“
“Sustained research efforts over the last 50 years have revealed

a considerable amount of information about immunity to taeniid cestode infections in the parasites’ intermediate hosts. As a product of this research, a series of effective recombinant vaccines have been developed which have no parallel in any other group of parasitic organisms. There are, however, many important aspects relating to immunity that remain to be elucidated. Some concepts have come to be firmly held as Pexidartinib solubility dmso facts and yet the supportive data are either conflicting or unconfirmed. This review considers the phenomenon of immunity to re-infection with taeniid cestodes in their intermediate hosts, examining carefully the nature of the evidence that is available to support conclusions that have been drawn in this area. “
“Replacement therapy with exogenous factor VIII (FVIII) to treat haemorrhages or used in prophylaxis induces inhibitory anti-FVIII immunoglobulin G (IgG) in some patients with haemophilia A. Therapeutic strategies to prevent

the onset of the deleterious anti-FVIII immune response are still lacking. Maternal IgG is transferred to the offspring during fetal and neonatal life. While protecting the offspring from bacterial and viral infections, maternal IgG may alter the repertoires of T and B lymphocytes, and may impair vaccination in early infancy. Using CHIR-99021 cell line haemophilic mice, we demonstrate that the transfer of maternal anti-FVIII IgG modulates the onset of anti-FVIII inhibitory IgG in early adulthood. The protective effect is reproduced upon reconstitution of naive mice with anti-FVIII IgG, see more suggesting that the reduced ability to mount an anti-FVIII immune response is the result of an interference between circulating anti-FVIII IgG and the administered FVIII rather than to a profound remodelling of lymphocyte repertoires occurring during the ontogeny of the immune system. Administration of exogenous factor VIII (FVIII) to patients with haemophilia A leads, in up to 30%

of the cases, to the development of neutralizing anti-FVIII alloantibodies that inhibit the pro-coagulant activity of FVIII. Different therapeutic strategies are being used to eliminate FVIII inhibitors, such as the administration of B-cell-depleting anti-CD20 antibodies (Rituximab®, Genentech Inc, South San Francisco, CA, USA) or the induction of immune tolerance upon repeated injection of high doses of FVIII.1 In patients, prophylaxis has been proposed as one of the rare solutions towards a reduction of the risk for the onset of the deleterious anti-FVIII immune response.2,3 During fetal life, maternal immunoglobulin G (IgG) of the IgG1 subclass is delivered through the placenta to the fetus via interactions with the neonatal Fc receptor (FcRn).

The key mechanism was not NK-cell depletion but depletion of CD8+CD122+ T cells. Adoptive transfer of exogenous CD8+CD122+ T cells to TMβ-1-treated mice rescued animals from severe disease. Moreover, transfer of preactivated CD8+CD122+ T cells prevented EAE development and significantly reduced IL-17 secretion. Naïve effector CD4+CD25− T cells cultured with either CD8+CD122+ T cells from wild-type mice or IL-15 transgenic mice displayed lower EPZ015666 order frequencies of IL-17A production with lower amounts of IL-17 in the supernatants when compared with production by effector CD4+CD25− T cells

cultured alone. Addition of a neutralizing antibody to IL-10 led to recovery of IL-17A production in Th17 cultures. Furthermore, coculture of CD8+CD122+ T cells with effector CD4+ T cells inhibited their proliferation significantly, suggesting a regulatory function for IL-15 dependent CD8+CD122+ T cells. Taken together, these observations suggest that IL-15, acting through CD8+CD122+ T cells, has a negative regulatory role in reducing Ruxolitinib cost IL-17 production and Th17-mediated EAE inflammation. “
“Forkhead box protein 3 (FoxP3+) regulatory T (Treg) cells and interleukin (IL)-17-producing T helper 17 (Th17)

cells have opposing effects on autoimmunity, as the former are crucial for maintaining self-tolerance while the latter play a key role in precipitating inflammatory autoimmune diseases. Here we report that Bacillus-derived poly-γ-glutamic acid (γ-PGA) signals naive CD4+ T cells to promote the selective differentiation of Treg cells and to suppress the differentiation of Th17 cells. The γ-PGA inducibility of FoxP3 expression was due partially to transforming growth factor (TGF)-β induction through a Toll-like receptor Coproporphyrinogen III oxidase (TLR)-4/myeloid differentiating factor 88 (MyD88)-dependent pathway. However, this pathway was dispensable for γ-PGA suppression of Th17 differentiation. γ-PGA inhibited IL-6-driven induction of Th17-specific factors including signal transducer and activator of transcription-3 (STAT-3) and retinoic acid-related orphan receptor γt (RORγt) while up-regulating the STAT-3 inhibitor

suppressor of cytokine signalling 3 (SOCS3). Importantly, in vivo administration of γ-PGA attenuated the symptoms of experimental autoimmune encephalomyelitis and at the same time reduced Th17 cell infiltrates in the central nervous system. Thus, we have identified the microbe-associated molecular pattern, γ-PGA, as a novel regulator of autoimmune responses, capable of promoting the differentiation of anti-inflammatory Treg cells and suppressing the differentiation of proinflammatory Th17 cells. These findings draw attention to the potential of γ-PGA for treating Th17 cell-mediated autoimmune diseases. Mechanisms for maintaining self-tolerance in the periphery include the activity of forkhead box protein 3 (FoxP3+) regulatory T (Treg) cells [1,2].