Deterioration

of the renal allograft function after the biopsies was seen in 31 patients (62%), of which 11 lost their graft. We suggest that histopathological changes of transplant glomerulopathy might be accompanied by inflammation of the microvasculature, such as transplant glomerulitis and peritubular capillaritis, thickening of the peritubular capillary basement membrane, and circulating anti-HLA antibodies. C4d deposition in the PTC is not always present in biopsy specimens of TG. We speculated that C4d deposition in the GC, rather than that in the PTC might be a more characteristic manifestation of TG. Many of the patients with TG had a history of AR. Anti-HLA antibody Class II, particularly when the antibody was DSA Class II, appeared to be associated with the development of TG. The prognosis of grafts exhibiting TG was not too good even under the currently used immunosuppressive protocol. Transplant glomerulopathy (TG) is Temozolomide price a morphologic pattern of chronic kidney allograft injury and is

generally associated with poor renal allograft survival.[1] TG is characterized by double contours of the glomerular basement Fulvestrant membranes (GBM), often accompanied by increased mesangial matrix.[2] TG is included as a criterion of chronic active antibody-mediated rejection (c-AMR) in the Banff ‘09 classification.[3] In this report, we discuss the clinical and pathological analyses of patients developing TG after renal transplantation. During the period from January

2006 to October 2012, TG was diagnosed in 86 renal allograft biopsy specimens (BS) obtained from 50 renal transplant recipients who were followed up at our institute. The data of these 86 BS and 50 patients were retrospectively reviewed from the clinical records in this study. The immunosuppressive protocol mainly consisted of triple-drug therapy, including methylprednisolone (MP), cyclosporine (CYA) or tacrolimus (TAC) and mizoribine (MZ), azathioprine (AZ) or mycophenolate mofetil (MMF) (Table 1). In some cases, basiliximab and rituximab had been given in addition (Table 1). Renal allograft biopsy was performed as part of the diagnostic workup for graft dysfunction Thymidine kinase and proteinuria, or as protocol biopsy. The biopsy specimens were examined by light, electron and immunofluorescence microscopy. The biopsies were diagnosed and scored according to the Banff ‘09 classification.[3] TG was diagnosed by light microscopy based on the finding of double contours of the GBM.[2] Patients with hepatitis C virus-associated glomerular disease and thrombotic microangiopathy were excluded from this study. We used the ptcbm score, which showed thickening of the peritubular capillary basement membrane and was evaluated by light microscopy (LM) in place of diagnosing of peritubular capillary basement membrane multilayering (PTCBMML) by electron microscopy (EM).

[16] in which leptomeningeal and intracortical vessels are scored separately. Each section was assessed in a semiquantitative manner using a four-point scale (Grades 0–3): Grade 0 = no Aβ positive vessels Grade 1 = mild (that is, scattered involvement of a few vessels) Grade 2 = moderate (strong circumferential staining in a few vessels or scattered positivity in some vessels) Grade 3 = severe (widespread strong circumferential

staining) Attems et al. [16] employed a further grade of 4 to describe very severe vessel involvement with dyshoric change. However, in the present study, such cases were assigned Grade 3. The assessment Maraviroc cost protocol was further extended selleck kinase inhibitor to separately record the presence and severity

(1; mild, 2; moderate, 3; severe) of capillary amyloid deposition (capillary CAA). SP were scored as both diffuse and cored plaques according to their density (that is, severity). Diffuse deposits were those that appeared homogenous, irregularly shaped and without a well-demarcated outline or core. Cored plaques tended to be symmetrical in shape, well demarcated, and had a ‘cored’ appearance with a compacted central mass of Aβ. The severity was again assessed on a four-point scale (Grades 0–3): Grade 0 = absent Grade 1 = mild (few plaques in most low power (×10) fields) Grade 2 = moderate (moderate number to many plaques in all lower power (×10) fields) Grade 3 = severe (many plaques in all high power (×25) fields Following semiquantitatively grading of each section, four patterns of Aβ deposition (types 1–4) were defined microscopically according to the presence and distribution of Aβ within SP and/or CAA (see results). For every case, each topographical region

(frontal, temporal and occipital respectively) was assigned a specific phenotype (1, 2, 3 or 4), before and thereby each case was designated by a three digit code (that is, 122, 112, 222 etc.) according to the type of histological change present in each brain region. The semiquantitative data were entered into an excel spreadsheet and analysed using Statistical Package for Social Sciences (SPSS) software (version 17.0). Nonparametric testing (Kruskal–Wallis) was used to compare the semiquantitative ratings for SP (diffuse and cored), and CAA (leptomeningeal, parenchymal and capillary) across the four pathological phenotypes. Statistical significance was accepted at P < 0.05 level. When statistically significant, post-hoc analysis (Dunn’s test [17]) was performed with Bonferroni correction for multiple comparisons. Consequently, the corrected ‘P value’ level for this test was set at P < 0.0083. Group comparisons of age at onset, age at death, duration of illness and brain weight were made using anova, with post-hoc t-test being employed where results were significant.

Additionally, CFSE-labelled splenic CD4+ T lymphocytes from C57BL/6 mice treated with or without AZM for 3 days were cultured in MLR with allogeneic BALB/c BM-derived mDCs for 3 days. It was confirmed that expression of major histocompatibility complex (MHC) class II and co-stimulatory molecules (CD40, CD80 and CD86) on LPS-induced mDCs was elevated in comparison with imDCs (data not shown). We did not observe any differences in the dividing CFSElow CD4+ population between AZM-treated and untreated C57BL/6 mice in the allogeneic MLR (Fig. 3c). These data indicate that AZM does not inhibit donor lymphocyte functions ex vivo at the tested doses. Novel immunomodulatory agents

focused on NF-κB in host DCs [6-11, 20-22, 31] instead of the Tipifarnib datasheet conventional immunosuppressants targeted on donor T lymphocytes [1-5] have been reported to prevent or attenuate GVHD in allogeneic haematopoietic transplantation, including https://www.selleckchem.com/products/XL184.html in the histoincompatible setting. In this study, we used AZM – a macrolide antibiotic and a NF-κB inhibitor of murine DC maturation – alone for GVHD prophylaxis and showed that it inhibited acute GVHD significantly in MHC-incompatible bone marrow transplantation (BMT) without interfering with donor engraftment. AZM is active against a wide variety of bacteria and also acts as an anti-inflammatory agent by modulating the functions of DCs, monocytes

and/or macrophages [24, 35-37]. Previously, Sugiyama et al. [35] and our team [24] have reported that AZM inhibits the maturation and functions of murine bone marrow-derived DCs in vitro. We also showed that AZM, by inhibiting the NF-κB pathway in LPS-stimulated DCs and generating DCs with regulatory DC properties, blocks murine DC–T lymphocyte interaction in allogeneic immune systems [24]. In murine allogeneic

BMT models, recipient-type regulatory DCs, characterized by low expression levels of co-stimulatory molecules, moderate levels of MHC molecules, low production of IL-12, high production of IL-10 and Olopatadine suppression of NF-κB activity even after stimulation with LPS, inhibited acute GVHD, mediated partly by IL-10, as a key regulator of anti-inflammatory responses [38, 39]. Sato et al. [38] also found that recipient-type regulatory DCs increased donor-type regulatory T cells (Treg) which produced IL-10 and resulted in protection from lethal acute GVHD. Additionally, we reported significantly increased IL-10 levels in co-cultures of allogeneic T lymphocytes and AZM-treated DCs [24]. The precise mechanisms underlying the findings presented in this report are unknown, because we did not analyse induction of Treg and/or plasma IL-10 of recipient mice treated with AZM, or for immunophenotypic or functional changes in DCs derived from recipients treated with AZM due to a numerical problem without in-vivo expansion stimulated with Flt3 ligand and/or other cytokines [11, 40, 41].

S1). In our next experiments, we used live FITC-conjugated S. aureus (strain SH1000) to investigate

the effect of PAR2-cAP alone or together with IFN-γ on the phagocytic activity of human monocytes and neutrophils this website against viable bacteria. We found that PAR2-cAP (1 × 10−4 m) or IFN-γ (100 ng/ml) alone enhanced phagocytic activity (Fig. 1a–d; a,b for neutrophils and c,d for monocytes). Although IFN-γ already appeared to stimulate phagocytic activity of monocytes at a concentration of 10 ng/ml, these effects were not statistically significant (Fig. 1c,d). Interferon-γ at a higher concentration (100 ng/ml) also enhanced phagocytic activity of human monocytes and neutrophils. The effects of IFN-γ at a concentration of 100 ng/ml reached statistical significance AG-014699 order (Fig. 1a–d). Stimulation with IFN-γ increased the number of FITC-positive human monocytes (49 ± 13% of change compared with untreated cells) and FITC-positive human neutrophils (41 ± 7% of change compared with untreated cells). The MFI also increased in IFN-γ-treated human monocytes (increased by 53 ± 14%) and neutrophils (increased by 80 ± 18%) compared with untreated controls. PAR2-cAP led to an increase in the amount of FITC-positive monocytes (increased by 35 ± 7%) and FITC-positive

neutrophils (increased by 24 ± 4%) compared with untreated samples. The MFI also increased in monocytes treated with PAR2-cAP (increased by 38 ± 8%) and in neutrophils (increased by 38 ± 4%) compared with untreated control samples.

The combined action of PAR2-cAP and IFN-γ using the same concentrations did not enhance the phagocytic activity of neutrophils or monocytes beyond that triggered by either agonist acting alone (Fig. 1a–d). Interferon-γ is a well-known endogenous modulator of phagocytic bacteria killing and secretory activity of human neutrophils and human monocytes.25,26 As an exogenous activator, LPS also affects phagocytic activity of both cell types. We wondered whether PAR2-cAP stimulation might interfere with LPS-modulated phagocytic activity of human neutrophils and monocytes. However, PAR2-cAP stimulation of human neutrophils as well 17-DMAG (Alvespimycin) HCl as monocytes did not enhance the LPS-induced phagocytic activity against S. aureus (see supplementary material, Fig. S2). Hence, despite the fact that PAR2-cAP alone up-regulates the phagocytic activity of human neutrophils and monocytes against S. aureus, this agonist failed to enhance IFN-γ-induced and LPS-induced phagocytic activity. We next investigated whether treatment of isolated human neutrophils with PAR2-cAP alone or in combination with IFN-γ affects the bactericidal activity of these phagocytes. In accordance with biosafety limitations, we used live E. coli bacteria in our experiments to estimate neutrophil killing activity.

Palliative care services in conjunction with the primary care and renal teams should play a role in educating community members in how they can support the person and the family, thus helping to meet the person’s choice of place to ‘finish up’ and helping family/community members feel they have appropriately supported the patient in the ‘finishing up’ process. As recommended by the American Society of Nephrology, Galla[9], there is a clear need to strengthen partnerships between palliative care and renal services if the best care and support is to be provided for a person opting for the non-dialysis pathway. Choice of place of death: being able to ‘finish up’ in the place of

their choice is very important to many indigenous Australians, with strong connections to traditional lands playing an important cultural role. However cultural practices https://www.selleckchem.com/GSK-3.html and requirements may vary from

community to community, and even within communities (particularly in urban areas). If a patient wishes to stay on or return to their homeland to die, these arrangements will need to Maraviroc be planned and supported. The effectiveness of renal supportive care may also strongly correlate with issues such as: person not being able to fully understand their illness; difficulties in communication and the length of time it takes to gain a person’s trust. Each indigenous person is different and therefore should not be stereotyped. One should not make assumptions of ATSI people and remember that each case is considered on an individual basis, without prejudice or judgement. Establish a commitment to the patient, build trust and be consistent. Respect ATSI cultural protocols, practices and customs. Respect ATSI decision-making processes. For most indigenous people having the family involved is extremely important. Families, next as mentioned above can include an extensive range of relatives. However there are individual variations.

Institutions such as hospitals and dialysis units, nursing homes must take responsibility for facilitating culturally competent care. This includes knowing the groups that most frequently use the institution, seeking out and disseminating information about cultural beliefs that might affect attitudes towards illness and health care, providing adequate translation services, and identifying community resources. Hiring and training health care workers (at all levels) who are members of the ethnic group in question or knowledgeable about them and who have credibility within these communities may assist greatly in bridging the cultural chasm. Health professionals need to acknowledge the beliefs and practices of people who differ from them in age, occupation or social class, ethnic background, sex, sexuality, religious belief and disability.

doi.org/10.1002/eji.201041377http://dx.doi.org/10.1002/eji.201141436http://dx.doi.org/10.1002/eji.201141682 “
“Antigen-loaded dendritic cells (DCs) used as anticancer vaccine holds promise for therapy, but needs to be optimized. The most frequently described DC vaccine is being matured with a cocktail containing prostaglandin

E2 (PGE2DC). However, even though PGE2DCs express both costimulatory and migratory receptors, their IL-12p70-prodcution is low, leading to an insufficient Th1 immune response. As an alternative, α-type-1 polarized DCs (αDC1s) have shown a superior production of IL-12p70 and subsequent activation of effector cells. From chronic lymphocytic leukaemia https://www.selleckchem.com/products/R788(Fostamatinib-disodium).html (CLL) patients, αDC1s can be generated to induce a functional Th1-immune response. Yet, another Temsirolimus molecular weight costimulatory receptor, CD70, appears to be essential for optimal DC function by promotion of T cell survival and function. So

far, PGE2 is suggested as one of the most important factors for the induction of CD70 expression on DCs. Therefore, we wanted to investigate whether αDC1s have the ability to express functional CD70. We found that CD70 expression on αDC1s could be upregulated in the same manner as PGE2DCs. In an allogeneic mixed leucocyte reaction, we found that antibody-blocking of CD70 on αDC1s from controls reduced effector cell proliferation although this could

not be found when using CLL αDC1s. Nevertheless, CD70-blocking of αDC1s from both controls and patients with CLL had a negative influence on the production of both IL-12p70 PIK3C2G and the Th1 cytokine IFN-γ, while the production of the Th2 cytokine IL-5 was enhanced. Together, this study further suggests that αDC1s should be considered as a suitable candidate for clinical antitumour vaccine strategies in patients with CLL. “
“Cytomegalovirus (CMV) infection has been implicated in accelerated T cell ageing. End-stage renal disease (ESRD) patients have a severely immunologically aged T cell compartment but also a high prevalence of CMV infection. We investigated whether CMV infection contributes to T cell ageing in ESRD patients. We determined the thymic output by the T cell receptor excision circle (TREC) content and percentage of CD31+ naïve T cells. The proliferative history of the T cell compartment by determination of the relative telomere length (RTL) and the T cell differentiation status was determined by immunophenotyping. It appeared that CMV infection did not affect thymic output but reduced RTL of CD8+ T cells in ESRD patients. Moreover, increased T cell differentiation was observed with higher percentages of CD57+ and CD28null CD4+ and CD8+ memory T cells. These CD28null T cells had significantly shorter telomeres compared to CD28+ T cells.

A monoclonal anti-human MBL antibody (HYB-131-01; Antibodyshop,

Copenhagen, Denmark) was used as the capture antibody. DNA Damage inhibitor A serum pool was used as a standard, where the level of MBL previously was quantified to 2800 μg/l by a MBL ELISA kit (Antibodyshop). A mouse biotinylated monoclonal anti-human MBL (HYB-131-01B; Antibodyshop) was used as the detection antibody, and development was by streptavidin–peroxidase and substrate (ABTS+H2O2). The lower detection limit of the assay was 18 μg/l. Cytokines.  Serum samples were analysed by Bioplex cytokine assays (Bio-Rad Laboratories, Hercules, CA, USA), according to the manufacturer’s protocol. Seventeen cytokine kits were obtained from Bio-Rad Laboratories. We analysed the sera for interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8,

IL-10, IL-12, IL-13, IL-17, G-CSF, granulocyte macrophage-CSF (GM-CSF), interferon γ (INFγ), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1β (MIP-1β) and tumour necrosis factor α (TNFα) (units: ng/l for all the cytokines). Statistical analyses.  Descriptive statistics are presented Luminespib cost as medians with ranges. Wilcoxon’s matched pairs signed rank sum test was used to test for changes over time in the laboratory values. The Mann–Whitney test was used to test for differences between the two groups receiving tobramycin once or three times daily. Associations between cytokines were measured with Spearman’s rank correlation. P-values < 0.05 were regarded

as statistically significant. No modifications were performed to adjust for multiple testing. Data analysis was performed using spss software (version 16, Chicago, IL, USA). The MASCC scores [1] varied between 19 and 23 both at the time of onset of febrile neutropenia and 1–2 days later (Table 1). Ninety-six and 92% of the patients had MASCC scores ≥21 at the onset of febrile neutropenia and 1–2 days later, respectively, suggesting a low risk of complications. The reductions in MASCC scores were all related to clinical symptoms deteriorating from none/mild to moderate. All patients, including the patients with decreased MBL values, had a non-complicated clinical course during the first couple of days of febrile neutropenia. Three patients had positive blood Isotretinoin cultures with streptococcus viridans, all sensitive to penicillin (minimum inhibitory concentrations (MICs) between 0.016 and 0.25 mg/l). The MICs to tobramycin were between 24 and 48 mg/l. One patient had growth of a Staphylococcus epidermidis in several blood culture bottles (with penicillin MIC 2 mg/l and tobramycin MIC 256 mg/l). The four patients with a positive blood culture had a similar non-complicated clinical course compared with the rest of the patients, with MASCC scores ≥21 and fever ranging from 38.4 to 40.1 °C. Two of them were considered to have moderate clinical symptoms and signs, and their highest PCT value was found to be 0.6 μg/l.

3,4 The repertoire of the CD8+ T-cell response is shaped by the entry of antigen into the major histocompatibility complex (MHC) class I processing pathway, binding MK-2206 price of peptides to MHC class I molecules and, ultimately, recognition of the trimolecular MHC–β2 microglobulin–peptide complex by CD8+ T cells. The interaction between the T-cell receptor (TCR)

and the MHC–β2 microglobulin–peptide complex is a two-step process. In the first step, the TCR docks on the MHC molecule in a peptide-independent fashion. This is followed by contact between the TCR and the peptide, which stabilizes the MHC–TCR complex.5 Therefore, at least two variables determine the outcome of antigen presentation by MHC class I molecules: (i) the nature of the presenting MHC class I allele and (ii) the amino acid (aa) composition of the nominal target peptide. Different peptides bind to the MHC molecule with different affinity and off-rate (the time of peptide binding to the MHC class I molecule), thereby affecting the magnitude and outcome of the priming phase, i.e. the close interaction

of antigen-presenting cells (APCs) and CD8+ T cells.6–8 A better understanding of AZD6738 the cellular immune response to Mtb will be of value in determining the nature of clinically relevant anti-Mtb immune responses, but also in gauging ‘vaccine-take’, for example for novel TB vaccines.9 Measuring cellular immune response induced by vaccination requires the identification of dominant and subdominant epitopes from individual Mtb proteins. The enumeration of antigen-specific T cells in TB infection is currently limited by inadequate knowledge of CD8+ epitopes. Some Mtb-specific Liothyronine Sodium CD8+ T-cell epitopes have been identified both in peripheral blood mononuclear cells (PBMCs) from Mtb-infected humans and in murine models.10,11 Yet, a broader peptide repertoire needs to be identified to appreciate the breadth of the CD8+ T-cell response. We choose the Mtb protein TB10.4 (Rv0288),

a component of several new TB vaccine candidates.12,13 TB10.4 is part of the 6 kDa early secretory antigenic target (esat-6) gene family, which encodes a number of secreted immunodominant molecules such as TB10.3 and TB12.9.14 Rv0288 is expressed both in virulent Mtb and BCG vaccine strains.14,15 A few CD8+ T-cell epitopes have previously been described for this protein,16,17 but a systematic approach covering the most frequent MHC class I alleles is lacking. In the current study, we used immobilized recombinant MHC class I molecules, covering a large part of the world’s population (approximately 95% of Caucasians, approximately 65% of Asians and approximately 40% of Africans),18 to define candidate epitopes from TB10.4 in a first screening step.

In addition to CHADS2 risk factors, other important beta-catenin activation risk factors like aggressive use of erythropoietin (EPO) agent, premature atherosclerosis and warfarin-induced vascular calcification contributing to thromboembolic

stroke should be taken into account in the process of stroke risk stratification. Stroke rate in HD patients with AF is in the range of 1.35–4.9 cases/100 patient-years; approximately twofold higher than HD cohorts with sinus rhythm. The combination of warfarin and antiplatelet agents likely to pose a higher bleeding risk and perhaps this practice should be avoided. The efficacy of warfarin for stroke prevention and the safety of anticoagulant mono-therapy have been poorly defined. Risk of bleeding associated with anticoagulant or/and antiplatelet therapy may be improved by optimizing current practice of DVT prophylaxis, use of heparin during dialysis, patients’ insight and compliance with medication, INR monitoring guidelines, periodical assessment of risk of fall and Ibrutinib datasheet application of user-friendly bleeding assessment tools. As there is complex interplay of pro-coagulant and anticoagulant factors in HD patients, which makes

them a higher risk of bleeding and clotting, it is very hard to draft firm guidelines. Extrapolation of guideline recommendation for anticoagulation in AF in the general population may not be appropriate for the HD population. From the available evidence it is clear that, there is significant increase in incidence of AF in the dialysis population and this is clearly associated with higher mortality compared with sinus rhythm, but there is increased risk of bleeding with warfarin use in this population and real evidence of benefit in stroke prevention and mortality reduction is lacking (Tables 3,5, 6).

Many clinicians are reluctant to prescribe warfarin HD patients with AF for preventing thromboembolic events and a large number of HD patients with AF are not anticoagulated.[39] Perhaps this reflects physicians’ fear of potential harm caused by warfarin treatment and their uncertainty about trading off risks and benefits of warfarin. It is worthwhile to assess practising nephrologists/cardiologists’ current opinion and practice of warfarin therapy for stroke prevention in dialysis learn more patients. Although randomized control trials can be logistically very hard to design because of the complexity of the HD patients with AF, there is an urgent need for randomized control trials by using objective risk/benefit assessment tools to really arrive at a decision regarding this complex issue. Currently, it is difficult to provide a recommendation purely based on evidence as it is limited. However, we recommend that, an individualized holistic approach be taken in all HD patients with AF optimizing all potential risk factors of bleeding and ischemic stroke.

On the other hand, expression of the M2 marker genes encoding Arg1, Ym1, Fizz1, MR and IL-13 was severely impaired in Jmjd3−/− BM macrophages cultivated in the presence of M-CSF to induce M2 polarization, indicating that Jmjd3 is critical for M2 marker gene expression in BM macrophages. Although M-CSF-induced BM macrophages or chitin-induced peritoneal macrophages showed severe defects in M2 macrophage www.selleckchem.com/products/midostaurin-pkc412.html marker expression in the absence of Jmjd3, Jmjd3−/− BM macrophages were capable of upregulating expression of genes representative of M2 macrophages in response to IL-4 stimulation. These findings indicate that Jmjd3-mediated H3K27 demethylation is dispensable for the generation

of M2 polarization in response to IL-4, and suggest that M2 macrophages should be further subcategorized depending on the requirement of Jmjd3. Jmjd3 contains an N-terminal tetratricopeptide repeat domain and the JmjC domain in the C-terminus 32–34. The expression of the C-terminal part of Jmjd3 containing the JmjC domain, but not its demethylase-defective mutant, was sufficient to rescue M2 marker expression in Jmjd3−/− BM

macrophages. Therefore, Jmjd3 functions as a demethylase to induce M2 macrophage polarization, although recent studies show EPZ 6438 a demethylase-independent role in controlling chromatin remodeling together with T-box family transcription factors 40. Chromatin immunoprecipitation-sequencing (ChIP-Seq) analysis revealed that, in general, trimethyl H3K27 was enriched in the promoter regions close to the transcription start sites in BM macrophages. H3K27 of M2 marker genes, such as Arg1, Ym1 and Mrc1, were not trimethylated in the presence Bay 11-7085 or absence of Jmjd3, suggesting that the M2 marker genes are not directly controlled by Jmjd3 through histone modification. On the other hand, H3K27 trimethylation of transcription factors such as Irf4 and Cebpb was differentially regulated by wild-type and Jmjd3−/− macrophages. The expression of Irf4 was diminished in Jmjd3−/− macrophages, and its expression was restored

in a Jmjd3 demethylase-dependent manner. Indeed, Irf4−/− mice showed severe defects in M2 macrophage polarization in response to chitin administration and induction of BM macrophages in the presence of M-CSF. Although Jmjd3 also controls a set of transcription factors, Irf4 is one of the critical target genes responsible for controlling M2 macrophage polarization (Fig. 2). Differential involvement of IRF transcription factors can be important for M1 and M2 macrophage polarization. It was reported that IRF5 is involved in the differentiation of M1 macrophages, though it is currently unclear whether Irf5 is epigenetically controlled by histone modifications 41. Jmjd3 is specifically involved in M2 macrophage polarization without affecting M1, despite the fact that Jmjd3 is TLR-inducible in macrophages.