After a single washing step in 1 × PBS and centrifugation, pelleted cells were resuspended in 200 μL PBS with polyclonal anti-CR3-RP antibody (diluted

1 : 100), and mAb OKM1 (diluted 1 : 10). Control samples were resuspended in mAb TIB111 (diluted 1 : 10 in PBS). After 1-h incubation in ice, unbound antibodies were removed by centrifugation and cells were resuspended in a precise volume of YNB medium with amino acids containing 0.9%D-glucose (cell concentration, 107 mL−1). A 100-μL aliquot of this suspension was then applied to 96-well plates R428 to undergo the adherence phase in biofilm formation for 30, 60, 90, and 120 min at 37 °C. At these time points, nonadherent cells were removed, adherent cells were washed with 1 × PBS in three washing steps and the viability of the adherent cells was evaluated by their ability to reduce 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) sodium salt to water-soluble formazan (Sigma-Aldrich). The parallel experiments were continued; after the adherence phase (90 min), nonadherent

cells were removed and adherent cells washed three times with 1 × PBS. Adherent cells were then overlaid with 100 μL of the new YNB medium and incubation continued at 37 °C for 48 h. The viability of the mature biofilm was evaluated as described above. Every experiment was performed in five parallel Fulvestrant in vitro wells and performed twice. The results were expressed as mean±SD.

Results were calculated as average±SD. Statistical significance in the difference between the samples was compared using Student’s t-test. A P-value of <0.05 was considered Anacetrapib significant, a P-value of <0.01 highly significant and a P-value of <0.001 extremely significant. Although the formation of a biofilm in the environment is a natural process important for the survival of many microorganisms, medical microbiology regards this complex structure as a serious complication during patient treatment or convalescence. Current trends in biofilm studies are aimed at possible ways to eliminate them, mainly via the application of antifungal agents (Kuhn et al., 2002; Al-Fattani & Douglas, 2004; Seidler et al., 2006; Borecká-Melkusová & Bujdáková, 2008). However, some authors have published different thoughts on biofilm treatment, such as photodynamic effects (Müller et al., 2007; Dovigo et al., 2009) or using antibodies (Rodier et al., 2003; Fujibayashi et al., 2009; Maza et al., 2009). In this study, we were focused on two different aspects: whether decreasing the ability of C. albicans to adhere to a plastic surface can reduce the production of the mature biofilm, and whether blocking the C. albicans surface antigen (CR3-RP) participating in adherence can significantly affect adherence, the first stage of biofilm formation. For experiments, one standard strain was selected, together with a C.

29 Interestingly, attenuated CD138+ plasma cell generation and Blimp-1 protein expression were discovered in Cox-2-deficient mouse B cells. This provides further evidence

that B-cell terminal differentiation is Cox-2-dependent. Although both Blimp-1 learn more and CD138 expression are attenuated in mouse B-cell cultures, this does not demonstrate that Blimp-1 is directly responsible for the decrease in the frequency of CD138+ cells. However, in the human B-cell cultures, Blimp-1 decreases early after Cox-2 inhibition and precedes CD38+ plasma cell precursor formation, suggesting that reduced Blimp-1 levels are responsible for decreased generation of human plasma cells. Blimp-1 is considered a master regulator of the plasma cell phenotype. Mice deficient in either Blimp-1 or Xbp-1 fail to generate significant numbers of plasma cells and produce relatively little serum antibody.3,26,30 We previously demonstrated that Cox-2-deficient mice immunized with HPV-16 virus-like particles displayed reduced neutralizing antibody titres and B-cell memory responses.15 Lupu et al.16 Apitolisib provide evidence that Cox-2 selective inhibitors impaired IgG production against T-dependent antigens, namely tetanus and diphtheria toxins. Autoimmune antibody production was also attenuated following treatment with Cox-2 selective inhibitors.31 These observations and our new in vitro results suggest that

impaired in vivo antibody production is a result of decreased B-cell differentiation to antibody-secreting plasma cells. Likewise, our results show reduced human Blimp-1 and Xbp-1 expression in the

presence of Cox-2 inhibitors, which is important in the decreased generation of plasma cell precursors (CD38+ antibody-secreting cells) and overall reduced antibody levels. Our results reveal that Cox-2 is essential for the differentiation B cells to antibody-secreting cells, providing a mechanism for for the involvement of Cox-2 in attenuated antibody production. Use of Cox-2 inhibitors during vaccination or infection could, therefore, impair the generation of plasma cells, which are important regulators of immunity. Without effective generation of plasma cells, patients may be more vulnerable to infections that rely on antibody-mediated immune responses, particularly elderly patients, who often take Cox-2 selective inhibitors and NSAIDs. Ultimately, our findings indicate that taking Cox-2 selective inhibitors or other NSAIDs that inhibit Cox-2 may reduce the efficacy of vaccines, as well as blunt immune responses to invading pathogens. The authors would like to thank Dr Ignacio Sanz and Tam Quach for providing T-cell-depleted human tonsil cells. This work was funded by the National Institutes of Health Grants DE011390, AI071064, ES01247 and the Training Program in Oral Sciences T32-DE007202. The authors have no conflict of interest. “
“Citation Romero R, Kadar N, Vaisbuch E, Hassan SS.

There was a significant main effect of the factor Object, F(1, 53) = 13.551, p = .001, η² = 0.203. The previously uncued objects were fixated significantly longer (mean of 0.414, standard error of 0.015) compared with the previously cued objects (mean of 0.328, standard error of 0.013). No effects were found for Cue Condition and Location. No interaction effects were found,

indicating that head and eye gaze cues yielded similar effects. The same infants that were tested in the eye-tracking experiment were also tested in a subsequent ERP experiment. The final sample PF-562271 manufacturer consisted of 46 infants (26 females) with an average age of 4 months and 16 days (age range: 4 months and 0–29 days; 23 infants for the eye gaze condition, 23 infants for the head condition). Forty-seven infants were excluded because of technical problems (N = 4), fussiness (N = 11) or poor data quality due to movement artifacts, and/or high impedances (N = 28). In the eye gaze condition, infants were presented with the same footage

DNA Damage inhibitor of the person as in the eye-tracking experiment. However, only one object was presented next to the head; therefore, the object was either cued or uncued by the person’s eye gaze. The person looked straight ahead for 1000 ms, then shifted gaze to the side (1000 ms). The last frame was held for 1000 ms. After a brief blank screen period (400–600 ms, on average 500 ms), only the object was presented again at the center of the screen (test phase, 1000 ms; see Figure 1 for an example of a trial). Different objects (N = 80) were used than in the eye-tracking experiment, but the same stimulus descriptions apply. ERPs for the previously cued objects are based on averaging 10–29 Acesulfame Potassium trials (mean of 16 trials), for the previously uncued object on 10–28 trials (mean of 16 trials). The same procedure was used in the head condition. As in the eye-tracking experiment, the person turned her head toward one of the objects while constantly keeping her eyes gazing toward the infant. ERPs are based on 10–30 trials (mean of 16 trials)

for the previously cued objects and on 10–27 trials (mean of 16 trials) for the previously uncued objects. A total of 160 trials were presented on a computer screen using the software Presentation (Neurobehavioural Systems, Inc., Albany, CA). EEG was recorded at 32 channels with a sample rate of 250 Hz using a BrainAmp amplifier (Brain Products GmbH, Munich, Germany). Signals were rereferenced to the linked mastoids, and a bandpass filter of 0.3–30 Hz was applied offline. Electrooculogram (EOG) was recorded bipolarly. ERPs were time-locked to the test phase and were assessed based on 1700 ms long EEG segments (including a 200 ms prestimulus baseline). Automatic artifact detection methods were applied using ERPLAB Software (http://erpinfo.org).

These data suggest that oestrogen contributes to the persistence of autoreactive T cells through the defective control of apoptosis, and may also provide a clue as to how oestrogen triggers SLE

activity. However, it remains unclear as to whether oestrogen affects the survival of peripheral T cells reactive to self-antigens in vivo. In addition, we did not examine the tripartite relationship among oestrogen, T cell apoptosis and disease activity in SLE patients. Further longitudinal study is required to clarify these issues. This research was supported by Basic Science Research Program through PD0325901 ic50 the National Research Foundation funded by the Ministry of Education, Science and Technology (No. 314-2008-1-E00113) and by a grant from the Korea Association of Internal Medicine. None. “
“Increased susceptibility to tuberculosis following

HIV-1 seroconversion contributes significantly to the tuberculosis epidemic in sub-Saharan Africa. Lung-specific mechanisms underlying the interaction between HIV-1 and Mycobacterium tuberculosis infection are incompletely understood. Here we address these questions by examining the effect of HIV-1 and latent M. tuberculosis co-infection on the expression of viral-entry receptors and ligands in bronchoalveolar lavage (BAL) of HIV-1-infected and -uninfected patients with and without latent M. tuberculosis infection. Irrespective of HIV-1 status, T cells from BAL expressed higher levels of the beta-chemokine receptor (CCR)5 than peripheral blood T cells, in particular the CD8+ T cells of HIV-1-infected persons showed elevated CCR5 expression. The concentrations of STA-9090 cost the CCR5 ligands RANTES and MIP-1β were elevated Interleukin-3 receptor in the BAL of HIV-1-infected persons compared with that in HIV-1-uninfected controls.

CCR5 expression and RANTES concentration correlated strongly with HIV-1 viral load in the BAL. In contrast, these alterations were not associated with M. tuberculosis sensitisation in vivo, nor did M. tuberculosis infection of BAL cells ex vivo change RANTES expression. These data suggest ongoing HIV-1 replication predominantly drives local pulmonary CCR5+ T-cell activation in HIV/latent M. tuberculosis co-infection. “
“Biofilm infections may not simply be the result of colonization by one bacterium, but rather the consequence of pathogenic contributions from several bacteria. Interspecies interactions of different organisms in mixed-species biofilms remain largely unexplained, but knowledge of these is very important for understanding of biofilm physiology and the treatment of biofilm-related infectious diseases. Here, we have investigated interactions of two of the major bacterial species of cystic fibrosis lung microbial communities –Pseudomonas aeruginosa and Staphylococcus aureus– when grown in co-culture biofilms. By growing co-culture biofilms of S. aureus with P.

This association between polymorphous CT60 allele and higher

MK2206 thyroid autoantibody levels might also be reflected indirectly in the association between the polymorphous CT60 allele and the hypothyroid form of PPT, where patients present with higher thyroid autoantibody levels. Concordantly, in our study only G-allele carrying genotypes were found among hypothyroid PPT patients positive for both thyroid peroxidase antibodies and thyroglobulin antibodies. The present results of an association between the CTLA-4 gene and thyroid autoantibody concentrations support previous findings provided by different genetic and epidemiological studies. With a whole genome linkage study the CTLA-4 gene has been recognized as a major thyroid autoantibody susceptibility gene [5], which has been confirmed subsequently in an expanded data set [16,17]. The studies on twin pairs indicated a higher prevalence of thyroid autoantibodies in healthy twin siblings [18] and

provided the estimation that a 73% likelihood of being thyroid autoantibody-positive might be attributed to genetic susceptibility [4]. Furthermore, in monozygotic twins the concordance rates of thyroid autoantibodies were higher than in dizygotic twins [19]. Also, according to several family studies, positive thyroid autoantibodies appeared more frequently in the first-degree relatives of AITD patients [20–22]. Although our data confirm a strong association between genotype and thyroid autoantibody production, limitations of the study based on the sample size should be considered. A larger sample size Dabrafenib research buy would decrease the risk of false negative or false positive results, especially in the evaluation of variables with minor effects. In spite of the strong influence of CT60 SNP on thyroid autoantibody production, the results of our recent study did not confirm the association of CT60 with HT or PPT, as the frequency of the G allele was 56·3% or 57% compared to 51·7% in the control population

[13]. Similarly, the association with Cyclin-dependent kinase 3 HT has not been established in the Japanese population [23,24]. However, an earlier study of a large group of Caucasian HT patients indicated CT60 as the HT susceptibility gene [7], and a similar finding has been reported recently in a small group of Slovak children [25]. Furthermore, a large meta-analysis, based on six published and unpublished studies of a total of 839 HT cases, indicated a significant association of CT60 SNP with HT [8]. As suggested by Ueda et al., the underlying mechanism by which CT60 triggers thyroid autoimmunity might be the reduced efficiency of splicing leading to a decrease of soluble CTLA-4 product and impaired CTLA-4 function [7]. This observation has not been supported by subsequent studies [26,27]. Another mechanism might be the linkage disequilibrium of CT60 with one or more nearby-lying polymorphisms, which alter CTLA-4 expression and function at the level of transcription, translation, mRNA stability or splicing [28].

Further evaluation of available techniques to establish compromises to save time, without sacrificing data quality ensued. The use of techniques to monitor the microcirculation is a recent development in investigative medicine, and has grown almost exponentially over the last 75 years. In detailed mechanistic studies, methods that can distinguish between changes in structure, function, endothelium dependent or independent function, and deep vs. superficial vascular beds have been developed, each with its own advantages and limitations

[12,14]. These techniques give highly reproducible and specific results; however, they are usually time-consuming, making click here them impractical for large studies. The ideal measure

of microcirculation should be able to noninvasively give continuous reproducible measurements, independent of tissue characteristics, and provide a result in a relatively short timescale. Furthermore, if they are to transfer to clinical practice, techniques must provide readily comprehensible results with minimal intervention. The application of laser Doppler fluximetry to the skin meets these criteria, and is used progressively more in the clinical fields of dermatology and microvascular surgery in addition to being utilized increasingly in numerous research studies. As the skin is a thermoregulatory selleck inhibitor organ and can exhibit large fluctuations depending on environmental conditions, vascular function is normally assessed following the application of noninvasive fixed stimuli. The two stimuli most often used are heating to 42° (generating a maximal physiological hyperemia) and response to arterial occlusion (Post Occlusive Reactive Hyperemia). Maximum hyperemic response can be used as an indicator of the cutaneous microvessel capacity for vasodilatation in the face of injury, as microvascular vasodilatation in response to injury is an important part of

healing [49]. This technique uses a temperature-dependent sustained increase in skin blood flow CYTH4 to achieve maximum hyperemia. PORH is the sudden rise in skin blood flow above baseline or resting flux levels after the release of an arterial occlusion [32]. This increase in flow has been associated with vasodilatation due to vasoactive metabolites release, myogenic autoregulation, endothelial response, all resulting from the preceding ischemia and also the subsequent flow-mediated vasodilatation, which is as a result of increased shear stress on the endothelium [13]. Reactive hyperemia is therefore commonly used as a model for microvascular reactivity function, to indicate either reduction in vasodilator bioavailability or an enhanced vasoconstriction in response to tissue hypoxia [77]. The interrogation of the microvasculature with changing shear stress would enable the states of vasodilatory dysfunction to be elucidated [19].

In addition, we observed that the PKC activator, PMA, as well as a bacterial fermentation end product, butyrate, also regulated TSLP expression both at the mRNA and protein level. Moreover, a strong synergistic effect between PMA and butyrate

was observed. The latter effect may be physiologically relevant given the major biological function of butyrate as an energy source in the colon [30] as well as its function as an epigenetic regulator [31]. As expected, stimulation of IECs by IL-1 induced NF-κB translocation into the nucleus and TSLP transcription involving IKK-β activity as revealed by the specific inhibition induced by Bay 11–7082. Clearly, the functional importance of both p38 and PKA was also identified using SB203580 and H-89, respectively. Conversely, extracellular signal-regulated kinase (ERK) ACP-196 mw had little effect since UO126 barely inhibited TSLP transcription. We first postulated that both p38 and PKA may act independently of IKK-β involvement since their specific pathway inhibitors were effective in the presence of Bay 11–7082, whereas UO126 had no effect. However, when transient transfections were performed with a 4 kb TSLP-promoter region, mutated for NF2 binding site, the stimulatory effect of IL-1 was completely abolished;

thus Rapamycin research buy arguing for a NF-κB only dependent regulation. We present in Figure 7 our working hypothesis that can explain the overall results obtained in IL-1-dependent TSLP regulation. Considering that, in the presence of BAY 11–7082, the effects of both p38 and PKA inhibitors are still apparent, we can argue that, since BAY 11–7082 has an IC50 of 10 μM [32], at the concentration 20 μM used PI3K inhibitor in the current study, IKK-β may only be partly inhibited and that the remaining TSLP transcription activity is still mediated by IKK-β. This has been verified using a NF-κB-dependent SEAP reporter system [33]. In fact, at the 20 μM concentration, BAY 11–7082 only inhibited IL-1-dependent NF-κB activation

by about 60% in Caco-2 cells. To explain the effects of the p38 inhibitors, our hypothesis is that IL-1 is activating IKK-β by two separate modes; first via the classical IL-1 receptor associated kinase/TGF-β activated kinase (IRAK/TAK) dependent pathway and second via a MKK/p38-dependent pathway as revealed previously for IL-6 [34]. Thus, inhibition of p38 resulted in a decreased TSLP expression due to a reduced activation of IKK-β, and enhances BAY 11–7082 direct inhibitory activity. Considering the involvement of PKA, it has been shown that PKA can also interfere with the NF-κB pathway; indeed PKA was revealed to phosphorylate p65 in a cAMP-independent manner therefore increasing transcriptional activity [35]. Our results argue for a similar regulation of TSLP transcription in human IECs. Recently, TSLP has been shown to be regulated by NF-κB in both human and mice airway epithelial cells [16]. A site located at –3.

Tissues were incubated for 2 h on ice and then washed twice with excess PBS for 15 min each. Cryosections were generated from liver tissue harvested in Tissue-Tek which were then air dried, fixed with neutral-buffered check details formalin, blocked with 10% normal mouse serum/1% Triton X-100/1% Tween-20 and exposed to the following fluorescently labeled antibodies–CD8 allophycocyanin (clone

53–6.7, eBioscience, CA, USA), CD4 PE (as above), polyclonal rabbit anti-p22-phox (Santa Cruz Biotechnology, CA, USA), polyclonal Rabbit anti-iNOS (BD Transduction Laboratories, CA, USA) and anti-Rabbit 488 (Invitrogen, NY, USA). Sections were also exposed to Hoechst DNA stain. All sections were exposed to appropriate laser light using the Erlotinib datasheet Leica SP5 confocal (Leica Microsystems, Germany) and the light emissions detected using photomultiplier tubes (PMTs) of the appropriate bandwidth. Emission spectra were collected using sequential scanning to avoid spectral bleed-through.

The data were collected as Leica image files using LAS-AF version 2.2.1 software (Leica) and converted into TIFF using Fiji software (http://fiji.sc/wiki/index.php/Fiji). Sections were incubated with either CD4/CD8 and F4/80 antibodies or Ly6G and F4/80 antibodies. Lungs of experimental mice were perfused with cold saline containing heparin and placed in cold DMEM (Mediatech-Cellgro). Livers and spleens were taken directly from experimental mice and placed in cold DMEM. All organs were then sectioned using fresh sterile razor blades and placed in DMEM containing collagenase IX (0.7 mg/mL; Sigma-Aldrich) and DNase (30 μg/mL; Sigma-Aldrich) at 37°C for 30 min [49, 50]. Digested tissue was gently dispersed by passage through a 70 μm pore size nylon tissue strainer (Falcon; BD Biosciences); the resultant single-cell suspension L-gulonolactone oxidase was treated with Gey’s solution to remove any residual RBC, washed twice, and counted. The liver cells were further processed over a 40%:80% Percoll (GE Healthcare) gradient and then washed and counted. Cell suspensions were stained for surface markers, washed,

processed for intracellular staining using the eBioscience “Transcription factor staining buffer set” (eBioscience) according to the manufacturer’s instructions and then stained for T-bet. The antibodies were titrated for use and consisted of anti-CD3 (Clone 17A2) labeled with eFluor450, anti-CD4 (clone RM4–5) labeled with PerCP-Cy5.5, anti-CD69 (clone H1.2F3) labeled with PE-Cy7, anti-CD44 (clone IM7) labeled with allophycocyanin-eFluor780, and anti-T-bet (clone 4B10) labeled with PE (all from eBioscience). Data from stained cells were collected using Diva software on an LSRII flow cytometer (BD Biosciences) and analyzed using FlowJo software (Tristar) and the gating system is shown in Supporting Information Fig. 2A.

Cells were left in culture for 4 days in 5% CO2 at 40 °C. At day 4, EDTA (20 mm) was added to all wells to a final concentration of 2 mm EDTA. The plate was left for 10 min in the CO2 incubator at 40 °C to detach cells from the well. Finally, each sample was mixed by carefully pipetting up and down before transferring

it to FACS tubes. Flow cytometry.  Staining was carried out in tubes by adding 110 μl cell suspension to 90 μl of FACS buffer (0.2% BSA, 0.2% sodium azide, 0.05% normal horse serum in PBS) containing CD4-RPE (Clone CT4) and CD8α-APC (Clone CT8 or Clone 3-298) or CD8α-RPE (Clone EP72 or Clone 3-298). All antibodies were purchased from SouthernBiotech (Birmingham, AL, Fludarabine mw USA). In addition, propidium iodide (Fluka BioChemica, Buchs, Switzerland) was added to exclude dead cells. Cells were incubated at 4 °C for 15 min and then washed once with 2 ml FACS buffer by centrifugation at 295 g for 5 min. All flow cytometry analyses were

performed on a BD FACSCanto™ (BD Biosciences, San Jose, CA, USA) equipped with a 488-nm blue laser and a 633-nm red laser. Using the FACSDiva software, we aimed at collecting a minimum of 10,000 live cells from each sample. Titration of all antibodies was performed prior to the experiment in order to determine the optimal staining concentrations, Selumetinib molecular weight and the multicolour panel was carefully evaluated using fluorescence minus one (FMO) controls [15]. Statistical analysis.  Antigen-specific stimulations were run in triplicates with the exception of the experiment where the effect of anticoagulant and type of serum were tested, as this experiment was run in duplicates. For all optimization steps Sodium butyrate and for experiment 1, the mean percentage of proliferated cells ± SE was calculated and shown. The CFSE proliferation data for experiment 2 were tested using standard anovaF-tests on a 5% significance level, with dose and breeding line as the classification variables. Normally, blood is stabilized with heparin, and FBS is used as an additive to growth medium

in cellular stimulation assays. We wanted to test EDTA as a substituent for heparin as anticoagulant in the blood samples and autologous serum from an NDV-vaccinated chicken (CIS) as a substituent for FBS in the cell culture medium used for our recall proliferation assay assessed for both CD4+ and CD8α+ (Fig. 1A) T cells. The strategy for gating on CD4+ and CD8α+ T cells was debris exclusion on the Forward Scatter (FSC) – Side Scatter (SSC) dot plot followed by exclusion of dead cells by PI staining. Out of the live cells, CD4 cells were gated positive at the PE axis and CD8α cells were gated positive at the APC axis in a PE-APC dot plot (Fig. 1A). Finally, the CD4+ and CD8α+ T cells were shown in a dot plot with CFSE on the x-axis, and the percentage of proliferated CD4+ and CD8α+ T cells were measured. Fig. 1B shows the results from one representative sample.

As such, the non-coding regulatory component of the genome (~ 9·7 × 107 base pairs in C. elegans, and 3 × 109 in humans) is an appealing environment for integrating signals into spatio-temporal and cell-type-specific gene expression patterns to confer diverse cellular function.[3] Chromatin Palbociclib concentration accessibility at non-coding DNA—namely, proximal promoter sequences—was described first by Carl Wu[4] in 1980 and was suggested to facilitate recruitment of factors that regulate gene activity. Contemporary understanding of mammalian regulatory DNA elements places the majority at

intronic or intergenic regions. However, unlike promoter studies, a major challenge of approaching the possibility of regulatory function in such distal DNA elements was determining where to look. Based on the observation that transcription only occurs at rearranged immunoglobulin heavy chain (Igh) genes, and never at non-rearranged genes, Susumu Tonegawa, Walter Schaffner and colleagues hypothesized that rearrangement brought downstream regulatory DNA into proximity with the promoter Lorlatinib solubility dmso sequence to enhance transcription. Indeed, in 1983, they described a downstream endogenous

enhancer element in the Igh gene that was active in a tissue-specific manner – in B cells, not in HeLa cells or fibroblasts.[5, 6] Recent advances in high-throughput sequencing technologies have improved our capacity to study and appreciate the role of the regulatory genome in controlling differentiation and cellular diversity. For example, mapping of chromatin accessibility and transcription factor binding sites demonstrates that ~ 1–2% of the genome is accessed as regulatory DNA in a given cell type. The cell-type-specific and largely non-overlapping nature of the regulatory DNA suggests that a substantial amount of intergenic sequence could encode regulatory information.[7] New genomic experimental approaches allow for incisive study of the role of Tolmetin this extensive regulatory DNA landscape in cellular differentiation. Differentiation of T helper (Th) and regulatory T (Treg) cells from

mature CD4 T-cells represents relatively late-stage differentiation. Although these cells can be considered close relatives, their faithful differentiation and phenotypic stability are critical, as their dysregulation can result in a broad spectrum of diseases, from autoimmunity to immunodeficiency. Th and Treg cell states are defined by expression of master regulator transcription factors [GATA binding protein 3 (GATA3), T-box 21 (TBET), RAR-related orphan receptor γ(RORγt) and Forkhead box P3 (FOXP3)] and associated phenotypic characteristics such as participation in particular types of inflammatory responses or the suppression of immune cell activation. Appropriate lineage stability or plasticity is encoded in the mechanisms instructing and maintaining the Th/Treg lineage-specific transcriptional programmes.