1) with moderate Roxadustat ic50 interstitial inflammatory cell infiltrate and moderate tubulitis. There was also evidence of moderate peritubular capillaritis. Electron microscopy and fluorescence failed to show evidence of viral inclusions

and stains for BKV, CMV or HSV were negative. Immunofluorescence was negative for C4d. Because of concerns about rejection in the face of possible ongoing viral nephropathy and possible nephrotoxicity from cidofovir, intravenous immunoglobulin (IVIG) was administered at 1 mg/kg weekly and the cidofovir stopped. Over the following 3 days, her fever settled immediately and her creatinine, after peaking at 339 μmol/L, begun to fall sharply. By day 5 her creatinine had fallen to 175 μmol/L, she remained afebrile and her systemic malaise had improved. Her creatinine timeline and therapy as shown in Fig. 2. Discharged home for convalescence, the patient continued to receive a further 3 weekly doses of IVIG (1 mg/kg) Hydroxychloroquine in vitro and her creatinine continued to fall such that 3 weeks post biopsy the creatinine was 127 μmol/L. Adenovirus PCR remains positive in the urine and respiratory secretions however have been undetectable in the serum and plasma since the last day of cidofovir. Repeat transplant

biopsy at day 98 did not show ongoing vascular rejection or viral inclusions but there was a mild ongoing cellular Immune system infiltrate. These cases illustrate the potential severity of adenovirus infection in kidney transplant recipients, and highlight the need for consideration of adenovirus infection as a cause of fever of unknown origin in such patients. They also illustrate that disseminated adenovirus infection can present early as well as late from the time of transplantation. Both cases also illustrate the potential renal toxicity of cidofovir. Adenoviral disease is well characterized in haematopoietic stem cell transplant (HSCT) recipients, with incidence ranging from 3% to 47%.[1] Reported clinical syndromes include pneumonia, colitis, hepatitis, haemorrhagic

cystitis, tubulointerstitial nephritis and encephalitis. Disease is often disseminated, and the mortality rate for symptomatic patients approaches 26%.[2] However adenovirus is a rare pathogen in solid organ transplant recipients. In kidney transplant recipients, the most common manifestation is hemorrhagic cystitis which both of our patients presented with. A recent literature review[3] revealed 37 reported cases, 36 of which occurred within 1 year of transplantation. Thirty-four patients received high-dose steroids for treatment of symptoms of acute rejection. Four patients received antiviral medications. Disease was mild and self-limiting in all and no patient required dialysis. There was universal return of creatinine to near baseline.

In addition, we were not able to assess differences between participants and non-participants, because information on personal characteristics such as age, socioeconomic status and periodontal status among the non-participants was not available. Our subjects were probably not a representative sample of Japanese women in the general population, however. As an example, educational levels were higher in the current study population than in the general population. According to the 2000 population census of Japan, the proportions CP-673451 nmr of women aged 30–34 years in Fukuoka Prefecture with <13, 13–14, ≥15 and an unknown

number of years of education were 52.0%, 31.5%, 11.8% and 4.8%, respectively [28]. The Dinaciclib datasheet corresponding figures for the current study in the control group were 20.7%, 33.2%, 46.1% and 0.0%, respectively. The present population might therefore have had a greater awareness about health than the general population. Nevertheless, the distribution of all 4

SNPs under study was consistent with Hardy–Weinberg equilibrium, and the selection bias associated with genotype distribution would be negligible. Although adjustment was made for a variety of potential confounders, residual confounding could not be ruled out. Additionally, it is possible that our results remain confounded by other potentially important factors such as a history of diabetes mellitus and dietary intake of vitamin D and calcium. In the current study, oral examinations were performed by dental hygienists. The dental hygienists were given detailed criteria for performing the examinations, but they received no specific training aimed at standardizing the procedures. In addition,

no reliability assessment of measurements was carried out in the present study. Therefore, it is unknown whether intra- and interexaminer consistencies were established. The current study size was rather small for a valid genetic association study, although a significant association was detected between SNP rs731236 and periodontal disease. The lack Miconazole of significant relationships between the other SNPs and periodontal disease, and the significant interaction between SNP rs731236 and smoking might be attributable to an insufficient statistical power. Furthermore, correction for multiple testing, an appropriate element in initial exploratory analyses, was not performed in this study. As this is a hypothesis-testing study and as part of the current findings is a replication of previously published results, we think that correction for multiple testing would cause us to underestimate our results. Our present study showed that VDR SNP rs731236 is significantly associated with the risk of periodontal disease.

Differential expression of HLA-DR was used to distinguish macrophages (CD16+DR+) and neutrophils (CD16+DR–) and the expression of galectins Inhibitor Library was studied in both subpopulations. A low level of eosinophil counts (< 3%) was observed in samples from both asmathic patients and healthy donors (see Table 2). As shown in Fig. 2a, gal-1 and gal-9 were expressed only on macrophages, while gal-3 expression was detected on both

macrophages and neutrophils. Differential gal expression by macrophages and neutrophils was also confirmed by immunofluorescence staining of sputum cell samples (Fig. 2b). Next, we compared galectin expression between asthma patients and healthy controls. Surface expression of gal-1 and gal-9 was clearly diminished in asthma patients compared with the control group (P < 0·05) (Fig. 3a,b), which is consistent with the BIBW2992 order reported action of these proteins as negative regulators of the immune responses [22, 23]. Surface expression of gal-3 was highly variable, and although it tended to be lower in asthmatic patients, this difference did not reach statistical significance (Fig. 3b). Gal-1, gal-9 and especially gal-3 have been linked to allergic conditions. However, we did not find any difference in gal expression between atopic and non-atopic asthma patients, indicating that the lower expression of gal-1 and

gal-9 is independent of atopic status (Fig. 3c). In addition, no significant differences in galectin expression were observed when patients were classified according to the dose of inhaled corticosteroids (Supplementary Table S2). Next, we explored the role of gal-1, gal-3 and gal-9 in the cytokine production induced by LPS. PBMC were stimulated with LPS in the absence or presence of gal-1, gal-3 and gal-9 during 24 h. RT–PCR assays showed that gal-3 reduced the expression of IL-12A induced by LPS (Fig. 4a). When samples were matched it was observed that the reduction of IL-12A

levels occurred in four of five samples tested; however, statistical analysis did Mirabegron not show any significant differences (Supplementary Fig. S2a). Gal-9 also caused a mild inhibition of IL-12B in four of five samples included (Fig. 4a and Supplementary Fig. S2b). In addition, we observed a slight increment of TNF-α expression in PBMC stimulated with LPS in the presence of gal-9. However, analysis of matched samples showed that this effect occurs in only three of five samples (Fig. 4a and Supplementary Fig. S2c). Regarding IL-1β, we did not detect any significant difference among treatments (Fig. 4a). Conversely, both gal-1 and gal-9 were able to increase the expression of LPS-induced IL-10 mRNA; in both cases the induction of IL-10 expression was observed in all samples tested (P = 0·01 and P = 0·03, respectively; Fig. 4b and Supplementary Fig. S2d).

In this process, phenomena described following observational 5-Fluoracil datasheet studies in humans drives hypotheses to be tested in animal experiments.

Animal experimentation in turn refines hypotheses that can then be tested in humans. This in turn leads to further questions and more productive animal experimentation. In this iterative approach, studies in humans and animals complement each other and can synergize to move our understanding of disease forward. That being said, my bias is that a good animal is not meant to primarily replicate all of what happens in humans, nor is it meant to be directly transferable. A well-working model generates logical and testable hypotheses that are consistent first foremost with existing data in the animal, and possibly in humans as well. The drive for those who primarily use animal models should be to ‘know thy model’, able to communicate

it effectively to others, and to generate productive integrative and iterative study. In studies in humans, several properties are taken into consideration to determine the appropriateness of the group of patients accessed for a study. These properties may be related to certain demographics or to Bcl-2 inhibitor prevalence of disease. When considering animal models to study adverse pregnancy outcomes, several issues come to mind. With decreasing funding through federal and other sources, Leukotriene-A4 hydrolase cost may play a large role in the choice of mode. Larger animal

models are likely more costly and research based on these models is receiving less support.[1] However, certain strains of genetically manipulated mice are also very expensive (http://jaxmice.jax.org). The animal welfare regulatory requirements for non-human primate work are increasingly stringent as is the administrative oversight. Another constraint is the ability to deal with the public relations issues necessary to utilize primate models. Only certain institutions have the capacity, specialized facilities, and highly trained veterinary staff. Depending on the species, there are some zoonotic disease issues that require a very rigorous occupational health program. Another practical issue related to choice of animal models is the presence of experts working with that model. Just as it is often better to watch a relative cooking a family tradition, rather than relying on a recipe, there are likely to be small bits of ‘inside’ or not widely published information about the model that are more easily obtained by direct contact with the investigator utilizing the model. Current thinking would refute the notion that the placenta is just a passive membrane between mother and fetus. Early studies of nutrient uptake suggest that most of the resources delivered to the uterus are utilized by this organ. The placenta is selfish.

TLR-2, -4, -5 and -11 are expressed on the cell surface while TLR-3, -7, -8 and -9 locate in endosomal compartments. They detect a broad range of pathogen-associated molecular patterns (PAMPs) to recognize different microbial as a means to distinguish ‘non-self’ from ‘self’, and in some cases they also recognize endogenous ligands, which are considered damage-associated molecular patterns (DAMPs) [2,3]. For example, TLR-4 can be activated by lipopolysaccharide (LPS) from Gram-negative bacteria, heat shock proteins and the anti-cancer drug taxol [4]. TLR-2 can be activated by the yeast cell wall component zymosan and lipoteichoic

acid from Gram-positive NVP-LDE225 bacteria. TLR-3 is activated by double-stranded RNAs from viruses, and TLR-9 recognizes cytosine-guanine dinucleotide (CpG) DNA motifs present in viruses and bacteria [5]. It is well known that activation of TLRs on APCs initiates a cascade of intracellular signalling events, resulting ultimately in enhancing antigen presentation, the production and release of inflammatory cytokines and up-regulation of adhesion and co-stimulatory molecules on the cell surface of APCs as well as priming the adaptive immune system [6–8] (Fig. 1). However, FK866 recent studies have shown that T cells also express certain

types of TLRs [9,10]. TLRs can function as co-stimulatory receptors that complement T cell receptor (TCR)-induced signals to enhance effector T cell proliferation, survival and cytokine production [11]. TLRs U0126 research buy could thus be involved in the modulation of the adaptive immunity, including regulatory T cell (Treg)-mediated immune suppression and the induction

of different subtypes of effector T cells, particularly interleukin (IL)-17-producing cell [T helper type 17 (Th17)] differentiation in autoimmune diseases and other immune response processes [9]. In this review we summarize mainly recent advances about the novel mechanisms of TLRs for the homeostasis and function of different T cell subtypes. Engagement of pattern recognition receptors (PRRs) with their microbial ligands induces specific downstream signalling events, and thereby provides immediate first-line protection of the host from invading pathogens. This is mediated by a number of components of innate systems, including activation of the complement pathway, phagocytosis of microbes, the release of direct anti-microbial mediators and production of cytokines and chemokines that, collectively, instruct mechanisms to combat infection [12]. Several PRRs have been characterized in a number of different hosts, such as pathogen-resistance proteins in plants [13,14], the Drosophila Toll protein [14,15] and TLRs in Caenorhabditis elegans and mammals [15,16]. During the last decade, many microbial motifs sensed by TLRs and their impact on the induction of first-line host responses have been demonstrated [9,16–18].

6B). This was not due to the toxicity of the inhibitors, since cellular AZD6244 cell line viability as measured with the dye MTT was not affected (Supporting Information Fig. 5A). CD1a expression was not altered (data not shown). The results so far indicated that IL-6 and IL-10 are important for the induction of the TLR-APC phenotype. Both cytokines

are known to signal via STAT-3. We therefore analyzed expression and phosphorylation of STAT molecules (STAT-1, -3, -5 and -6). The STAT activation pattern of iDCs and TLR-APCs differed significantly (Fig. 7): differentiation of DCs in the presence of R848 resulted in an almost constitutive activation of STAT-3. In contrast, STAT-1 tyrosine phosphorylation was much shorter compared to STAT-3 phosphorylation (1 h–day 1). Regarding STAT-6 activation no significant differences between TLR-APCs and iDCs were detected (data not shown). In contrast, during the whole differentiation process, STAT-5-activation dominated in iDCs and was much lower in TLR-APC. Hence, the comparison of the STAT activation pattern in iDCs and TLR-APCs revealed a prevailing STAT-5 activation in iDCs and a dominant STAT-3 activation in TLR-APCs. To further corroborate the link between STAT-3 activation and expression

of CD14 and PD-L1, we performed blocking experiments of STAT-3 with the chemical inhibitor JSI-124. After addition of JSI-124 expression of CD14 was not sustained (Fig. 8A) and upregulation of PD-L1 expression was Forskolin cost prevented (Fig. 8B). CD1a expression was unaffected (data not shown). Treatment with the inhibitor JSI-124 did not

compromise cell viability (Supporting Information Fig. 5B). To close the link between STAT-3 activation and induction of PD-L1 expression we used chromatin immunoprecipitation (ChIP) assay to determine the ability of STAT-3 to bind to the PD-L1 promoter. We found that STAT-3 was rapidly recruited to the PD-L1 promoter (Fig. 8C). Since STAT-1 is known to be involved in PD-L1 expression too Ergoloid and since STAT-1 was also activated we checked the binding activity of STAT-1 to the PD-L1 promoter (Fig. 8D). However, we found that STAT-1 binding was minor compared to STAT-3 and nearly no differences in STAT-1 binding between iDCs and TLR-APCs were detectable. From the results so far, we concluded that STAT-3 has a central role for the formation of the TLR-APC phenotype. On the other hand, inhibition of MAPKs with the pharmacological inhibitor SB203580 (MAPK p38) and UO126 (MAPK p44/42) had the same effect as STAT-3 inhibition: the failure to sustain expression of CD14 and the prevention of PD-L1 expression. To link both effects with each other, we tested whether suppression of cytokine production (especially of IL-6 and IL-10) after MAPK inhibition influenced the status of STAT-3 activation. After combined blockade of p38 and p44/42 tyrosine phosphorylation of STAT-3 was reduced markedly. The same pattern was found when LPS instead of R848 was used to induce TLR-APC (Fig. 9A).

Such documents are peer-reviewed, but not copy-edited or typeset. They Antiinfection Compound Library cell line are made available as submitted by the authors. “
“We hypothesized that

the aberrant expression of microRNAs (miRNAs) in rheumatoid arthritis (RA) T cells was involved in the pathogenesis of RA. The expression profile of 270 human miRNAs in T cells from the first five RA patients and five controls were analysed by real-time polymerase chain reaction. Twelve miRNAs exhibited potentially aberrant expression in RA T cells compared to normal T cells. After validation with another 22 RA patients and 19 controls, miR-223 and miR-34b were over-expressed in RA T cells. The expression levels of miR-223 were correlated positively with the titre of rheumatoid factor (RF) in RA patients. Transfection of Jurkat cells with miR-223 mimic suppressed Selleckchem MLN8237 insulin-like growth factor-1 receptor (IGF-1R) and transfection with miR-34b mimic suppressed cAMP response element binding protein (CREB) protein expression by Western blotting. The protein expression of IGF-1R but not CREB was decreased in RA T cells. The addition of recombinant IGF-1-stimulated interleukin (IL)-10 production by activated normal T cells, but not RA T cells. The transfection

of miR-223 mimic impaired IGF-1-mediated IL-10 production in activated normal T cells. The expression levels of SCD5, targeted by miR-34b, were decreased in RA T cells after microarray analysis. In conclusion, both miR-223 and miR-34b

were over-expressed in RA T cells, but only the miR-223 expression levels were correlated positively with RF titre in RA patients. Functionally, the increased miR-223 expression could impair the IGF-1-mediated IL-10 production in activated RA T cells in vivo, which might contribute to the imbalance between proinflammatory and anti-inflammatory cytokines. “
“We set out to determine whether intravenous immunoglobulin (IVIG) improves in vitro fertilization (IVF) success rates in women with a difficult history of multiple (≥2) prior IVF failures and /or ‘unexplained’ infertility. A total of 229 women with multiple IVF failures (3.3 ± 2.1) and/or unexplained infertility (3.8 ± 2.7 years) were given IVIG on the day of egg retrieval, and the subsequent IVF success rates before were compared with published success rates from the Canadian database (CARTR). The pregnancy rate per IVIG-treated cycle was 60.3% (138/229), and the live birth rate per IVIG-treated cycle was 40.2% (92/229). This is a significantly higher success rate compared to the Canadian average (30% live birth rate; CARTR statistics from 2010; P = 0.0012). In cases where a single embryo was transferred, pregnancy rate using IVIG was almost twofold the CARTR pregnancy rate [(61%(20/33) to 34.9% (428/1225)]. In cases where two high quality (≥Grade 3) day 5 blastocysts were transferred, nearly a 100% pregnancy rate was achieved using IVIG (30/31).

The yeast species were identified by morphological features and commercial characterisation kits. From 54% of the specimens, we isolated 122 strains representing 29 yeast species. Debaryomyces hansenii, Candida lambica and Candida krusei were the most frequently isolated species. We found a plethora of yeasts in birds living in proximity to humans, whereas birds living in more remote areas were colonised with a lower number of fungal species. “
“Dermatophytosis caused by Microsporum canis is a heterogeneous disease with variable clinical manifestations. M. canis is a zoophilic dermatophyte and the most frequent fungi isolated from dogs, cats and children in

Brazil. The aim of this study was to investigate the genetic variability of M. canis isolates from buy AZD1208 different animal species using two microsatellite markers, namely, McGT(13) and McGT(17), and to correlate the results with the clinical and epidemiological patient data in Brazil. The study included a global set of 102 M. canis strains, including 37 symptomatic cats, 35 asymptomatic cats, 19 human patients with tinea, 9 asymptomatic dogs and 2 symptomatic dogs. A total of 14 genotypes were identified, and 6 large populations were distinguished. There was no correlation between selleck kinase inhibitor these multilocus genotypes and the clinical and epidemiological data, including the source, symptomatology, clinical picture, breed, age, sex, living

conditions and geographic location. These results demonstrate that the use of microsatellite polymorphisms is a reliable method for the differentiation of M. canis strains. However,

we were Phosphoglycerate kinase unable to demonstrate a shared clinical and epidemiological pattern among the same genotype samples. “
“The aim of this study was to evaluate oral epithelial cells of the oral mucosa infected by Candida albicans using exfoliative cytology. Oral smears were collected from clinically normal-appearing mucosa by liquid-based exfoliative cytology of 60 individuals (30 patients with oral candidiasis and 30 healthy controls matched for age and gender) and analysed for morphologic and cytomorphometric technique. Morphologically, candida-infected epithelial cells exhibited nuclear enlargement, perinuclear rings, discrete orangeophilia, and cytoplasmic vacuoles. The cytomorphometric analysis demonstrated that the cytoplasmic area (CA) of the epithelial cells was diminished in patients undergoing candidiasis as compared to the non-infected controls. In addition, there was an augmentation in nuclear area (NA) and NA/CA area ratio. This study revealed that oral mucosa of patients undergoing candidal infection exhibited significant changes in the size and shape of the oral epithelial cells. “
“Fusarium species are common hyaline soil saprophytes and plant pathogens that are opportunistic fungal pathogens of immunocompromised patients.

The infected mice displayed a significant up-regulation in the expression of chemokines (Cxcl1, Cxcl2 and Ccl2), numerous pro-inflammatory cytokines (Ifng, Il1b, Il6, and Il17f), as well as Il22 and a number of anti-microbial peptides (Defa1, Defa28, Defb1, Slpi and Reg3g) at the site(s) of infection. This was accompanied by a significant influx of neutrophils, LY294002 order dendritic cells, cells of the monocyte/macrophage lineage and all major subsets of lymphocytes to these site(s). However, CD4 T cells of the untreated and C. difficile-infected mice expressed similar levels of CD69 and CD25. Neither tissue had up-regulated levels of Tbx21, Gata3 or Rorc. The caeca and colons of the

infected mice showed a significant increase in eukaryotic initiation factor 2α (eIF2α) phosphorylation, but neither the splicing of Xbp1 nor the up-regulation of endoplasmic reticulum chaperones, casting doubt on the full-fledged induction of the unfolded protein response by C. difficile. They also displayed significantly higher phosphorylation of AKT and signal transducer and activator of transcription 3 (STAT3), an indication of pro-survival signalling. These data

underscore the local, innate, pro-inflammatory nature of the response to C. difficile and highlight eIF2α phosphorylation and the interleukin-22–pSTAT3–RegIIIγ axis as two of the pathways that could be used to contain and counteract the damage inflicted on the intestinal Cobimetinib clinical trial epithelium. Clostridium difficile is a Gram-positive, spore-forming, anaerobic bacterium.[1] It is the most prevalent cause of infectious very diarrhoea in antibiotic-treated patients in hospitals.[2, 3] Infection with C. difficile can lead to a broad range of clinical outcomes, including asymptomatic colonization, mild diarrhoea and severe pseudomembranous colitis. Clostridium difficile encodes a number of toxins. Of these, two exotoxins, TcdA and TcdB, are the bacterium’s main virulence factors. Both toxins are glucosyltransferases that irreversibly inactivate small GTPases of the Rho family.[4, 5] This in turn leads to the depolymerization of the epithelial actin cytoskeleton, impaired function of tight junctions and severe epithelial cell damage.[6-8] The use of

ileal loop models has provided useful insights into the function of these toxins.[9] Studies using mouse models of C. difficile infection have proven the higher susceptibility of MyD88−/−[10] and Toll-like receptor 4−/−[11] mice and the protective effect of Toll-like receptor 5 stimulation against acute C. difficile colitis.[12] The higher susceptibility of MyD88−/− mice is at least in part due to impaired CXCL1 expression and the consequent reduction in neutrophil influx to the site of infection.[13] Interestingly, NOD1−/− mice also have reduced neutrophil recruitment to the site of infection, but show similar levels of epithelial damage as wild-type mice.[14] However, much remains to be determined about the host inflammatory and mucosal response to C.

Therefore STAT6 not only is a key regulator of GATA-3 expression, but further contributes to Th2 commitment by preventing the acquisition

of the Th1, Th17 or Foxp3+ Treg cell phenotypes.51 It is now clear that not only STAT6, but also STAT5 plays an essential role in the initial steps of Th2 differentiation. Indeed, expression of constitutively active STAT5 is sufficient to induce IL-4 expression in cells lacking STAT6 or cultured under Th1 polarizing conditions,52 whereas IL-2 neutralization or STAT5 deletion prevents IL-4 secretion.53 Both STAT5 and GATA3, target the hypersensitivity enhancer region HSII located in the second intron of the il4 gene,52,54,55 and synergize to promote IL-4 secretion. Finally, STAT5 also regulates il4rα expression56 (Fig. 3). HM781-36B purchase This suggests that not only IL-2 but also other cytokines signalling through STAT5,

such as thymic stromal lymphopoietin, may be as important as IL-4 in driving Th2 development, as summarized in Table 1. Both SOCS1 and SOCS5 inhibit IL-4 signalling36,57 (Fig. 3); indeed, SOCS1-deficient T cells secrete increased levels of IL-4.29,31 SOCS5 also inhibits Th2 differentiation,39 but the relevance of this remains controversial because SOCS5-deficient mice do not have increased susceptibility to atopy, perhaps reflecting the close homology and likely redundancy between SOCS4 and SOCS5.37 Interestingly, SOCS3 and SOCS2 also regulate Th2 polarization, positively and negatively, respectively. Indeed, constitutive expression of SOCS3 in T cells confers increased susceptibility Cisplatin mw in atopic models,33,39,58 while SOCS2-deficient mice develop exacerbated disease because of enhanced Th2 polarization.59 Surprisingly, neither SOCS3 nor SOCS2 seem to directly regulate IL-4 signalling. Instead, SOCS3 is a key regulator of IL-6-mediated or IL-23-mediated STAT360–62 and of IL-12-mediated STAT4 activation33 (Fig. 3), suggesting that SOCS3 may indirectly promote Th2 differentiation by preventing

the development of Th1 and Th17 cells. Similarly, SOCS2-deficient CD4+ T cells display reduced STAT3 activation and enhanced STAT5 phosphorylation and so SOCS2 probably inhibits Th2 differentiation much by inhibiting IL-2 signalling, while favouring the development of Th17 cells.59 Therefore, SOCS proteins control Th2 differentiation not only by inhibiting the activation of STAT6 and STAT5, but also by regulating the polarization of naive CD4+ T cells towards the other CD4+ lineages (Fig. 3). This is summarized in Table 2. T helper type 17 cells secrete high levels of IL-17A, IL-17F and IL-22 and play a key role at mucosal surfaces where they combat infection by extracellular bacteria. The Th17 cells are highly pro-inflammatory, and an alteration of the Th17 versus Treg cell balance is proposed as a potential mechanism that may induce autoimmunity.