Next, we set out to determine the phenotypic characteristics of NKG2C+CD56dim NK cells from the present patient cohort. Because our data suggested that expansion of NKG2C+ NK cells was dependent on HCMV infection, we choose to perform an aggregate analysis of NKG2C+ NK cells in patients with HCV and HBV. Significantly fewer Selleck BMN 673 NKG2C+ CD56dim NK cells expressed NKG2A, CD161, Siglec-9, and NKp30 compared with NKG2C− CD56dim NK cells (Fig. 1C). In contrast, NKG2C+

NK cells more commonly expressed ILT2, CD57, and CD2. Percentages or MFI of CD62L, CD8, NKG2D, CD16, and DNAM-1-positive cells were indistinguishable when comparing NKG2C+ and NKG2C− NK-cell subsets (Fig. 1C and Supporting Information 2). The expression pattern of cytolytic molecules in the granules of CD56dim NK cells revealed that both Granzyme A and perforin were expressed at equivalent levels in NKG2C+ and NKG2C− NK cell subsets. In contrast, expression of Granzyme B was higher and Granzyme K lower in NKG2C+, compared with NKG2C− NK cells (Fig. 1D). Importantly, the phenotype of NKG2C+ NK cells was identical in HCV- and HBV-infected individuals (data not shown). Together, these data show that NKG2C+ NK cells have a full cytolytic arsenal and a highly differentiated phenotype, as defined by the

high expression of CD57. To examine the functionality of the NK cells and its relation to their expression of NKG2C, we separated them into three subsets: NKG2A+NKG2C−, NKG2A−NKG2C−, and NKG2A−NKG2C+ NK cells. We simultaneously assessed these subsets Palbociclib manufacturer in the presence of various target cells for multiple functional responses. NKG2C+NKG2A− NK cells derived from patients with HBV or HCV infection displayed

stronger and more diverse functional responses than NKG2C− NK subsets following stimulation with targets expressing HLA-E, and against RAJI cells in the presence of anti-CD20 mAb (Fig. tuclazepam 2A). In agreement with the prominent role for NKG2A in NK cell education 8, 29, NKG2A+ NK cells responded better than NKG2A− NK cells, regardless of their NKG2C expression, against both MHC class-I-negative K562 and 721.221 target cells. Furthermore, NKG2A+ NK cells produced high levels of IFN-γ in response to stimulation with IL-12/IL-18 (Fig. 2B), while IFN-γ production was almost undetectable in the NKG2C+CD56dim subset. Together, these results demonstrate that NKG2C+ NK cells display a functional profile similar to highly differentiated NK cells, shown to have a high responsiveness via ADCC but poor ability to respond to exogenous cytokines 30, 31. Extending previous results, we here show that differentiated NKG2C+ NK cells are polyfunctional and respond strongly to specific stimulation by HLA-E expressing target cells. Of note, NKG2C+ NK cells were also present in the liver (Supporting Information 3A). NKG2C+ NK cells in the liver were mostly NKG2A− and responded to stimulation with HLA-E expressing 721.221 target cells but not against control 721.

Another important consideration click here in translating the in vitro murine data to the bedside is the dosing regimen. Serum concentrations of atorvastatin, for lipid lowering, are in the nanomolar range [42], while inhibition of T cell activation and MMP-9 production occurs only at micromolar concentrations in tissue culture. Direct comparisons of human serum concentrations to in vitro experiments are not appropriate, especially for a lipophilic drug such as atorvastatin. Additionally, previous

work has shown that statin treatment inhibits MMP-9 production indirectly in the vessel wall of abdominal aortic aneurysms [43,44], thus serum levels may not reflect accurately local tissue concentrations at work, similar to the disconnect between serum and tissue levels of MMP-9 in KD [45]. An altered lipid profile has been reported in children with KD. During the acute phase of disease a pro-atherogenic lipid profile [46,47], with a decrease BGJ398 supplier in total cholesterol, high-density lipoprotein-cholesterol (HDL-C), apoA1 and apoA2 and an increase in triglycerides and apoB, is observed [46,48,49]. Total cholesterol returns quickly to normal, but HDL-C recovery is slow and remains

significantly lower than expected up to years later [46]. In addition to the observed mild dyslipidaemia in patients with KD, arterial function may be abnormal with abnormal measures

of endothelial dysfunction even in those without aneurysms [50–53]. Carotid artery intima-media thickness among KD patients is greater, and endothelial dysfunction has been reported both in children with persistent coronary lesions as well as in those without detectable early coronary artery involvement, Methocarbamol indicated by decreased brachial artery flow-mediated dilatation [40,48,49,53]. Thus, all patients with KD, even in the absence of echocardiographic evidence of coronary artery involvement, may be at risk for premature atherosclerosis even if managed appropriately during the acute phase of the illness. The potential benefits of statin therapy are recognized outside the acute phase of illness. Recognizing the limitations of the in-vitro results reported, confirmation of the immunomodulatory effects of atorvastatin are needed in vivo using the LCWE-induced coronary arteritis animal model of KD. This model, which mimics accurately the histopathological changes seen in the coronary arteries of KD patients [19,20,54], provides a unique opportunity to study treatment protocols and potential side effects of statin therapy in young animals, providing important insight prior to human studies.

F. McDermott by FP7-HEALTH-2007-2.4.4-1 grant; both G. Cook

and M. F. McDermott are supported by the Charitable Foundation of the Leeds Teaching Akt targets Hospitals and the Arthritis Research Campaign (arc). Conflict of interest: The authors declare no financial or commercial conflict of interest. See accompanying Viewpoints: http://dx.doi.org/10.1002/eji.200940172http://dx.doi.org/10.1002/eji.200940039 “
“Inflammasomes are multi-protein platforms that drive the activation of caspase-1 leading to the processing and secretion of biologically active IL-1β and IL-18. Different inflammasomes including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLR caspase-recruitment domain-containing 4 (NLRC4) and absent in melanoma 2 (AIM2) are activated and assembled in response to distinct microbial or endogenous stimuli. However, the mechanisms by

which upstream stimuli trigger inflammasome activation remain poorly understood. Double-stranded RNA-activated protein kinase (PKR), a protein kinase activated by viral infection, has been recently XL184 shown to be required for the activation of the inflammasomes. Using macrophages from two different mouse strains deficient in PKR, we found that PKR is important for the induction of the inducible nitric oxide synthase (iNOS). However, PKR was dispensable for caspase-1 activation, processing of pro-IL-1β/IL-18 and secretion of IL-1β induced by stimuli that trigger the activation of NLRP3, NLRC4 and AIM2. 17-DMAG (Alvespimycin) HCl These results indicate that PKR is not required for inflammasome activation in macrophages. PKR, known as double-stranded RNA-activated protein kinase, is activated by viral infection and plays an important role in controlling viral spreading within the host [1, 2]. PKR contains an N-terminal dsRNA binding domain and a C-terminal kinase domain [3]. After activation by binding to viral dsRNA, PKR phosphorylates the translation initiation factor EIF2A to inhibit cellular RNA translation

leading to the inhibition of viral protein synthesis [1]. PKR can also modulate NF-κB signaling and cellular apoptosis [4, 5]. In addition, stimulation of TLR4 can trigger PKR-mediated apoptosis of macrophages, which allow some pathogens such as Bacillus anthracis to escape immune clearance [6]. PKR can also link pathogen sensing to stress responses in metabolic disease [7]. Notably, PKR has been recently implicated in the processing of caspase-1 and IL-1β secretion in response to diverse stimuli [8], suggesting that this kinase acts in a common step required for inflammasome activation. Inflammasomes are intracellular multi-protein complexes that drive the activation of the protease caspase-1 [9, 10]. To date, four bona fide inflammasomes have been identified, NOD-like receptor (NLR) family pyrin domain-containing 1 (NLRP1), NLRP3, NLR caspase-recruitment domain-containing 4 (NLRC4) and absent in melanoma 2 (AIM2), that link specific microbial or endogenous stimuli to caspase-1 activation [9, 10].

This is consistent with the fact that anti-IL-5 had no effect on expression of major pro- and anti-inflammatory cytokines in thyroids of IFN-γ−/− mice. To our knowledge, this is the first report using a murine thyroiditis model to address the role of IL-5 and eosinophils in autoimmune inflammation. Eosinophilia is a classic feature of several human diseases such as parasitic infections, selleck chemicals inflammatory bowel disease, asthma, Churg–Strauss syndrome, eosinophilic esophagitis and eosinophilic gastroenteritis.9,34–38 Eosinophils have many functions, including antigen presentation and exacerbation of inflammatory responses through their ability to secrete various

cytokines and lipid mediators.9,35 Eosinophils are important inflammatory cells, for example in sites of allergic R788 in vivo inflammation, and they have been shown to affect both tissue injury and remodelling,9,37,39 and they have been implicated in promoting fibrosis in several diseases.10–14 IL-5 regulates the activation, differentiation, recruitment and survival of eosinophils,9 and neutralizing

IL-5 can block infiltration of eosinophils into synovial tissues34 and sites of allergic inflammation.40 Although the role of IL-5 in the differentiation, proliferation and migration of eosinophils has been well established,9 it remains unclear how important IL-5 and eosinophils are to the development and/or progression of clinical diseases including autoimmune diseases. In fact, several clinical trials using anti-IL-5 mAb in patients with asthma have failed to improve symptoms, although IL-5 seems to be responsible for the accumulation of eosinophils in blood and tissues.41–43 In this study, we took advantage of the differential migration of eosinophils versus neutrophils to thyroids of IFN-γ−/− and WT mice ifenprodil during development of G-EAT to examine the potential role of eosinophil trafficking to sites of autoimmune inflammation in G-EAT induction and resolution. In this model, eosinophils contribute substantially to thyroid inflammation in IFN-γ−/− mice

with G-EAT, as they are one of the major cell types infiltrating IFN-γ−/− thyroids from day 10–21 after cell transfer.8 However, inhibition of the migration of most eosinophils to the thyroid by administration of anti-IL-5 had little effect on G-EAT severity scores. Although anti-IL-5 markedly reduced the contribution by eosinophils to thyroid inflammation, other cells such as neutrophils increased in number and the end result was a similar severity score (defined as the percentage of the thyroid replaced by infiltrating inflammatory cells) in thyroids of IFN-γ−/− mice given control IgG or anti-IL-5. Therefore, a similar degree of inflammation of the thyroid (severity score) can result from the activity of different inflammatory cells and cytokines or chemokines.

In some experiments, cell culture supernatants were analyzed using luminex protein array according to the manufacturer’s instructions (Millipore). The frequency of antigen-specific cytokine producers was determined following culture for 24 h in 96-well filtration plates (Millipore), with or without 50 μg/mL MOG35–55. Antibodies Small molecule library from eBioscience were: anti-IL-17 (TC11–18H10), biotinylated anti-IL-17 (TC11–8H4), IFN-γ (AN18), and biotinylated

anti-IFN-γ (R4–6A2). Streptavidin–alkaline phosphatase (Southern Biotech) and an alkaline phosphatase substrate kit (Vector Laboratories) were used to identify trapped cytokine. Spots were counted using the CTL ImmunoSpot Analyzer (Cellular Technology) with ImmunoSpot

software, and the number of spots in the medium-only wells subtracted to generate the data shown. Statistical analyses were performed using GraphPad Prism statistical analysis software. Group differences were analyzed by unpaired, two-tailed Students t-test. p-values of 0.05 or less were considered significant. This research was supported by a grant from the NINDS, NIH to B.M.S. (R01 NS057670) Y-27632 in vitro and by the National Multiple Sclerosis Society Grant FG 1985-A-1 (S. J. L.). The authors declare no financial or commercial conflict of interest. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. “
“Citation: Ghazeeri G, Abdullah L, Abbas O. Immunological differences in women compared oxyclozanide with men: overview and contributing factors. Am J Reprod Immunol 2011; 66: 163–169 Gender differences in the innate and adaptive immune systems have long been observed in humans. These immunological differences in immune function manifest as diverse susceptibilities to different types of infections and varied risks of developing autoimmune

disorders and maybe even, cancers. Several factors contribute to the development of this immunological dimorphism including sex hormones, genetic makeup, environmental causes, and more recently microchimerism. Although the aim behind this sexual immune dimorphism is still unclear, it is tempting to believe that the higher risk of developing autoimmune diseases in women somehow serves the higher evolutionary goal of reproduction and creating new life. “
“Pulmonary fibrosis is defined by an overgrowth of fibroblasts and extracellular matrix deposition, and results in respiratory dysfunction that is often fatal. It is the end stage in many chronic inflammatory interstitial lung diseases (ILD) such as sarcoidosis and idiopathic pulmonary fibrosis (IPF).

Recent theoretical work has suggested that immunopathology-induced disruption of the covariation between parasite density and host damage does not necessarily invalidate the trade-off model of parasite virulence, but it can substantially alter the evolutionary outcome [16-19]. Indeed, if immunopathology damage is an increasing function of parasite multiplication (the more the antigenic stimulus, the stronger the immune response), then parasites are predicted to evolve towards lower virulence because highly multiplicative strains will pay the cost of direct host damage plus the immunopathology-induced Daporinad cost. On the contrary, if immunopathology arises independently of parasite multiplication

(a starting signal is enough to

trigger immunopathology), then we expect parasites to become nastier because any prudent (slowly reproducing) parasite would nevertheless pay the immunopathology cost. Subsequent theoretical work has refined these predictions, showing that an additional important factor affecting the evolutionary outcome is how disease selleck severity is measured [19]. The task of the immune system is not necessarily to clear the infection. In many cases, it might be more rewarding to coexist with the parasite instead of declaring the war. Even though the two terms refer to different processes, infection tolerance and immunological tolerance do overlap to a certain extent [20]. As mentioned above, infection tolerance involves a wide array of mechanisms, including the down-regulation of many effectors that confer immunological tolerance (a nonresponsive immune system even when an antigenic stimulus is present). As for most immunological pathways, immunological tolerance involves different redundant mechanisms. Central tolerance operates during the negative selection of T cells with a very high affinity to self-MHC molecules occurring in the thymus; peripheral tolerance arises when self-reactive cells that have escaped the negative

selection are anergized or suppressed by regulatory T cells [21]. Anti-inflammatory cytokines produced by macrophages and regulatory T cells PD-1 antibody inhibitor also play a prominent role during the resolution of an inflammatory response and are essential components of organismal homoeostasis during an infectious insult [22]. Immunological tolerance is a mechanism that controls and prevents immunopathology. Tolerant hosts, thus, may pay a minimal cost of infection because they are protected by the immunopathology cost. Again this is likely to have substantial fitness consequences for the parasites and drive their evolution. For instance, when tolerance is due to a down-regulated immune response, parasites are freed from the selection induced by the host immune system that breaks down the antagonistic co-evolutionary interactions between the hosts and the parasites.

From December 2009 to August 2012,

we used this ALT chimeric flap to reconstruct two separate defects in upper extremity on five patients (mean age: 36.6 years; range: 15∼47 years). The locations of defect were Dabrafenib cell line palm and fingers in four patients and forearm in the other patient. The sizes of defect ranged from 4.5 × 1.5 cm to 20 × 10 cm. A minimum of two separate perforator vessels in the flap were identified. The skin paddle was then split between the two perforators to shape two separate paddles with a common vascular supply. There were no cases of flap failure or re-exploration. Four donor sites were directly closed and one was covered by a skin graft. Donor-site morbidity was negligible. The ALT chimeric flap provides customized cover for two separate defects in upper extremity. © 2013 Wiley Periodicals, Inc. Microsurgery 33:631–637, 2013. “
“Elbow reconstruction is challenging for reconstructive surgeons. The purpose of this report is to present the results of the use of freestyle perforator-based propeller flap designed from the medial arm region Selleckchem ZD1839 for elbow reconstruction. The defects following soft tissue sarcoma resection at the medial and posterior elbow were repaired in

two patients. The dimensions of the defects were 11 × 7 cm2 and 10 × 7 cm2. Two perforators were identified in each case using Doppler ultrasound probe in the medial arm, adjacent to the defect. The perforator with visible pulsation was chosen as the pedicle vessel, which was 12-cm and 7-cm proximal to the medial epicondyle. An elliptical flap, extending almost the full length of arm, was raised

and rotated 180° to repair medial elbow defects. The sizes of the flaps were 17 × 8 cm2 and 11 × 7 cm2. The donor sites were closed directly. Both flaps survived; temporary see more venous congestion occurred in one case. There were no other postoperative complications. These cases illustrated that the medial arm flap might be used for reconstruction of medial elbow defects with this freestyle perforator-based propeller flap design. © 2014 Wiley Periodicals, Inc. Microsurgery, 2014. “
“Skin graft is still a method of choice for the coverage of temporal defects. But there are some disadvantages like a “patch” appearance, the need of dressing or longer healing time. Numbers of local flaps have been described for closing skin defects on temporal region. Yet, they may cause distortion of the surrounding tissues, especially in the temporal hairline and eyebrow. We present a series of seven local flaps based on small branches (SB) of the superficial temporal artery (STA) for the coverage of temporal defects, and discuss their advantages. Supermicrodissection of SB of the STA was performed to obtain local flaps for reconstruction of temporal defects after skin cancer excisions in seven patients.

Also, we confirmed that CD161 is not expressed on NK92 cells using the DX12 anti-CD161 monoclonal antibody (Fig. 1B). CD161 expression on K562-CD161 clones was confirmed via flow cytometric analysis using the DX12 anti-CD161 monoclonal antibody (Fig. 2A,B). Compared to K562 transfected with the empty pCI-neo vector, K562-CD161 clone #3 (Fig. 2A) exhibits 51.4% surface CD161 expression, whereas K562-CD161 clone #12 (Fig. 2B) exhibits 66.9% surface CD161 expression. Flow cytometry confirms that K562 (data not shown) and NK92 do not naturally express CD161. When NK92 cells that were rested overnight without IL-2 and K562-CD161/-pCI-neo cells https://www.selleckchem.com/products/rxdx-106-cep-40783.html are co-incubated overnight in a

1:1 ratio, NK92 incubated with K562-CD161 consistently produce significantly greater amounts of IFN-γ than NK92 incubated with K562-pCI-neo. Additionally, two separate K562-CD161 clones exhibiting high (Fig. 2B) and low (Fig. 2A) levels of CD161 expression were employed as target cells. As we predicted, the K562-CD161 low expressing cells were associated with reduced IFN-γ production compared to K562-CD161 high expressing Fluorouracil order cells (Fig. 2C). To confirm this increase in IFN-γ production was associated with CD161 ligation

of LLT1 on NK92, we blocked CD161 on K562-CD161 with DX12 anti-CD161 monoclonal antibody and repeated our IFN-γ assay. Blocking K562-CD161 in this manner reduces associated IFN-γ production to levels comparable to that observed with K562-pCI-neo (data not shown). Taken together, these data indicate that NK92 express LLT1, and LLT1 is functional in the same manner as previously reported on the YT cell line and freshly isolated NK cells. With this in mind, we proceeded to analyse LLT1 signalling pathways using this NK92:K562-CD161 LLT1 ligation system. Except where indicated, in all instances K562-CD161 ALOX15 refers to the CD161 high expressing K562-CD161 clone. NK92 (rested overnight without IL-2):K562-CD161/-pCI-neo cells were co-incubated overnight and harvested at various times for RT-PCR analysis. IFN-γ mRNA was evaluated by PCR, and GAPDH was amplified to confirm

an equal amount of template was used for each reaction. We observed no significant difference in IFN-γ mRNA over the various time points in either the presence or absence of CD161 ligation (Fig. 3A,B). The calibrated density of IFN-γ mRNA divided by median calibrated density of GAPDH mRNA for NK92 incubated with K562-CD161 and K562-pCI-neo clearly demonstrates there is no increase or decrease in IFN-γ mRNA expression associated with LLT1 ligation and IFN-γ production (Fig. 3B). This suggests that IFN-γ production associated with CD161 ligation does not directly stimulate IFN-γ transcription. IFN-γ mRNA detected came from NK92 as K562 does not produce IFN-γ. This was confirmed by analysing K562 cDNA alone for IFN-γ mRNA (data not shown).

Prevalence of infection and parasitaemia were high in honeycreepers, and the infection induced a substantial drop in body mass, haematocrit

and finally high mortality [39-42]. https://www.selleckchem.com/products/Imatinib-Mesylate.html As a consequence, lowland areas that provided a favourable environment to the mosquito and therefore to Plasmodium transmission became unfavourable for the bird hosts, and the populations of several honeycreepers went eventually extinct in lowland areas and established refuges at high altitudes, where temperature is too low to allow mosquito survival [37, 38]. In 2002, a survey of Hawaiian honeycreepers in lowland areas found that the populations of the amakihi (Hemignathus virens) recovered in number, comprising from 24.5% to 51.9% of the avian community, in spite of very high prevalence (24–40% if estimated by microscopy, 55–83% if estimated by serology) [43]. Genetic structure of high- and low-altitude populations further suggested that individuals that recolonized low-altitude sites did not come from high-altitude refuges, but likely originated from residual lowland populations that were continuously exposed to malaria imposed selection [44, 45]. Finally, the finding that

prevalence was still high in this expanding population possibly suggests that tolerance rather than resistance rapidly evolved in amakihi (even though data on parasitaemia are needed to confirm this). Carbohydrate The rapid spread of resistance/tolerance to malaria SCH772984 in vitro also suggests that standing genetic variation was possibly present

in the amakihi, before the spread of malaria. It should be noted that amakihi was the only honeycreeper to show such evolved pattern of resistance, further stressing the among-host variability shown by experimental infections of European passerines [33-36]. Additional evidence for resistance to malaria parasites comes from population genetics studies focusing on immune genes involved in the antigen presentation process. Screening of genes of major histocompatibility complex (Mhc) class I and II in different European passerines has reported a protective role of Mhc diversity and specific alleles towards the infection with different Plasmodium lineages in terms of both prevalence and parasitaemia [46-48]. Moreover, when multiple populations were surveyed, alleles conferring a protective effect were found to be population-specific, suggesting a co-evolutionary interaction between the host and the parasite, potentially promoting local adaptation [49]. More recent work using next-generation sequencing has shown that distinct Mhc supertypes confer qualitative (prevalence) and quantitative (parasitaemia) protection against two Plasmodium species (P. relictum and P. circumflexum) in one wild population of great tits (Parus major) [50].

3). The ability of Mϕ to reduce T-cell responses has been documented for many years.32 In tumour models, this is thought to contribute to tumour escape from immunosurveillance, but it is unlikely that this represents a normal physiological expression of this process. In inflammation stimulated by infection, restricting T-cell proliferation within the tissue could have a role simply by sparing finite metabolic resources for other effector cells that are present. Rapid T-cell division is highly dependent on local glucose33 and activated Mϕ also consume glucose and other sources of metabolic ROCK inhibitor energy at a high rate.34,35 Therefore, limiting proliferation may be a form of immune system triage at the site of

inflammation. Another possibility is that restricting T-cell activation prevents the differentiation of antigen-specific T cells within tissues. Segregating the environment in which T cells differentiate, from that in which they exercise effector function, could reduce the generation of T-cell effector cells that can be activated by autoantigens. At a site of acute inflammation, Mϕ will be processing large amounts of damaged normal tissue that might lead to an increased risk of local autoimmunity. It is not, however, the case that T-cell immunity is entirely shut down in this inflammatory microenvironment.

Our demonstration that T cells removed from the presence of Mϕ can resume proliferation (Fig. 2) shows that T cells that traffic away from the inflammatory environment will still be able to contribute GSK2126458 to the pool of circulating activated antigen-specific cells. This local immune response could still serve to amplify T-cell responses and support the production of immunological memory. In terms of Mϕ function, our data suggest that a lack of TNFR1 signalling impedes the development of Mϕ with the capacity to inhibit T cells. This critical role for TNFR1 in the generation of these cells also suggests TNFR1 may be important to the generation of MDSC in tumours. Therefore, our study throws light on other previously unexplained findings: that in a model of metastasizing

lung carcinoma, although tumours initially expand at normal rates, in TNFR1−/− mice, metastases regress after 21 days.36 Also in TNFR1−/− mice and mice treated with TNFR1−/− bone marrow,37 there stiripentol is a reduced tumour burden in a model of colorectal carcinoma. We suggest that this may relate to a failure to generate functional MDSC. However, other factors also remain important, because the efficacy of TNF-α blockade, which has been used as a therapy in late-stage ovarian carcinoma, maps at least partially to a defect in TNFR1 signalling to T cells.38 The lack of TNFR1 was also associated with a lack of PGE2 production. It has been previously demonstrated that PGE2 is required for MDSC maturation in vivo.30,39 PGE2 can also modulate the function of dendritic cells as APCs, and this effect depends on expression of EP2 or EP4 by the dendritic cell.