By reporter assay, DDX3 helped IPS-1 up-regulate IFN-β promoter activation and knockdown of DDX3 by siRNA resulted in reduced IFN-β induction. This activity was conserved on the DDX3-C fragment. DDX3 only marginally enhanced IFN-β promoter activation induced by transfected TANK-binding kinase 1 (TBK1) or I-kappa-B kinase-ε (IKKε). Forced expression of DDX3 augmented virus-mediated IFN-β induction and host cell protection against virus infection. Hence, DDX3 is an antiviral IPS-1 enhancer. Retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are cytoplasmic RNA helicases 1–3, which signal the Cytoskeletal Signaling inhibitor presence of viral RNA through the adaptor, IFN-β

promoter stimulator-1 (IPS-1) (also known as mitochondrial antiviral signaling protein/caspase recruitment domain (CARD) adaptor inducing IFN-β (Cardif)/virus-induced signaling adaptor) to produce IFN-β 4–7. IPS-1 localizes on the outer membrane of the mitochondria via its C-terminus 6. Its N-terminus consists of a CARD domain, which interacts with the CARD domains of RIG-I and MDA5. Viral RNA resulting from penetration or replication are believed to assemble in the CARD-interacting helicase complex to activate the cytoplasmic IFN-inducing pathway. Although non-infected cells usually express minimal amounts of RIG-I/MDA5, the final output of type I IFN is efficiently

induced at an early stage of infection to protect host cells from viral Dasatinib purchase spreading. Once IPS-1 is activated, the kinase complex consisting of TANK-homologous proteins and virus-activated kinases induce nuclear Casein kinase 1 translocation of IFN regulatory factor-3 (IRF-3) to activate the IFN promoter 8. NAK-associated protein 1, TANK-binding kinase 1 (TBK1) and I-kappa-B kinase-ε (IKKε) are components of the kinase complex that phosphorylates IRF-3 to induce type I IFN 9, 10. RIG-I recognizes products of various RNA viruses, while MDA5 recognizes products of picornaviruses 1, 11. RIG-I and MDA5 share the helicase domain, which is classified into the DEAD (Asp-Glu-Ala-Asp) box helicase family, and the domain can bind to various RNA structures. 5′-triphosphate RNA or short dsRNA is a ligand of RIG-I, whereas long dsRNA is a ligand of MDA5 1,

12. However, these RIG-I-like receptors (RLR) are usually up-regulated to a sufficient level secondary to IFN stimulation, suggesting that other molecular mechanisms are responsible for the initial sensing of viral RNA. Here, we looked for molecules that bind IPS-1 by yeast two-hybrid, and found a DEAD box helicase, DDX3 (DEAD/H BOX 3), as a component of the complex of IPS-1. DDX3 facilitated IPS-1-mediated IFN-β induction to confer high antiviral potential on early infection phase of host cells. This is the first report showing that DDX3 is an IPS-1 complement factor for antiviral IFN-β induction in host infectious cells. IPS-1 is constitutively present on the mitochondrial membrane and plays a central role in the cytoplasmic IFN-inducing pathway.

The reduction in background risk of cervical cancer by elimination of the most important HPV types will affect cost-effectiveness of screening programmes and may, in the long term, allow increasing screening intervals. Co-ordinated quality assurance/monitoring of HPV vaccination and cervical screening is advisable for finding the most efficient strategies for cervical cancer control. Data on vaccination coverage will be essential for every country performing HPV vaccinations. HPV vaccination registries are

preferable, but sales statistics and serosurveys may be alternatives. For rapid assessment of vaccine programme efficacy, the continuous monitoring of which HPV types are spreading in the population Copanlisib chemical structure will become necessary for early monitoring of ‘type replacement’ phenomena, inappropriate vaccination strategies or other reasons for vaccination failure. Surveys in sexually this website active teenagers and/or in younger participants of cervical screening programmes should be contemplated. As HPV-associated cancers and condylomas are now vaccine-preventable diseases from now onwards they should be subject to similar surveillance strategies as other vaccine-preventable diseases.

The recent WHO recommendation on HPV vaccination (http://www.who.int/wer/2009/wer8415.pdf and http://www.who.int/immunization/documents/positionpapers/en/index.html#hpv) includes information that will help countries make decisions about how HPV vaccination fits into their strategy for cervical cancer control. The authors alone are responsible for the views expressed in this publication and they do clonidine not necessarily represent the decisions, policy or views of the World Health Organization or the funding agencies. The findings and conclusions in this report are those of the authors. “
“The use of biological agents combined with methotrexate (MTX) in rheumatoid arthritis (RA) patients has strongly improved disease outcome. In this study, the effects

of abatacept on the size and function of circulating B and T cells in RA patients not responding to anti-tumour necrosis factor (TNF)-α have been analysed, with the aim of identifying immunological parameters helpful to choosing suitable tailored therapies. We analysed the frequency of peripheral B and T cell subsets, B cell function and T regulatory cell (Treg) inhibitory function in 20 moderate/severe RA patients, according to the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, primary non-responders to one TNF-α blocking agent, who received abatacept + MTX. Patients were studied before and 6 months after therapy. We found that abatacept therapy significantly reduced disease activity score on 44 joints (DAS)/erythrocyte sedimentation rate (ESR) values without causing severe side effects.

79, which differed significantly from chance, t(13) = 3.92, p = .002. Infants produced an average of approximately 1.5 additional vocalizations during the impossible cube display above that of the possible cube display and the perceptual controls. This pattern of behavior was consistent in 10 infants, with two infants vocalizing equally and two infants vocalizing more during the possible cube display, Z = 2.72, p = .007. By contrast,

there were no reliable differences in vocalizations made during presentation of the possible cube versus the other perceptual control stimuli (all p-values > .68). The frequency of infants’ mouthing behavior toward each of the displays was also PD0332991 datasheet recorded. Interestingly, five infants engaged in mouthing behavior, Mitomycin C ic50 but only toward the impossible cube display, t(13) = 2.69, p < .02, and they did not use oral exploration for any of the other displays. This pattern of behavior was consistent in five of the infants, and nine infants did not engage in any attempted mouthing behavior, Z = 2.24, p = .02. We set out to examine the effects of a perceptual illusion on infants’ manual exploration. Our initial question of whether 9-month-olds would respond differently to picture displays of possible and impossible cubes received a

clear answer: Infants engaged in qualitatively similar types of reaching behaviors (e.g., touching, scratching, rubbing, and patting) toward the possible and impossible cubes as well as the nonobject pictorial control displays, but they directed a significantly greater number of these gestures toward the impossible object display. Thus, by 9 months of age, infants

use the pictorial depth cue of interposition to guide manual investigation of 2D depictions of objects, and they behave differently in response to pictures of possible and impossible objects. Presumably, it was the detection of anomalous depth information that inspired greater visual attention and more persistent manual exploration of the pictures of impossible objects. Perhaps the impossible figure invoked increased interest and exploration because the infants found the unusual geometry so novel and unlike any other objects they Teicoplanin had previously encountered in the world. The impossible cube display also elicited a reliably higher frequency of social referencing to the parent and experimenter, as well as a significantly greater number of vocalizations relative to the possible cube and perceptual control displays. Increased referential looking to the mother (a trusted source) and to the experimenter (a friendly female stranger in close proximity) may be due to the infants’ desire to gather applicable information about the unusual or ambiguous nature of the impossible cube stimulus.

6). This implies that TAMs in colorectal cancer possess a greater capacity to present antigen and co-stimulate T cells than TAMs in other cancers. To assess the functional capacity of colorectal TAMs in co-stimulating T cells, we performed an MLR assay. TAMs were sorted from colorectal co-culture spheroids and incubated

with allogeneic T cells for 4 days, after which T-cell proliferation was measured by tritiated-thymidine R788 solubility dmso incorporation. Indeed, the TAMs were highly competent at stimulating T-cell proliferation (Fig. 4B). Tumour cells sorted from the co-cultures were unable to stimulate T-cell proliferation, indicating that tumour cells per se do not possess T-cell co-stimulatory properties, and in vitro differentiated macrophages were poor stimulators. Together, these observations indicated that TAMs acquired T-cell co-stimulation capabilities during the co-culture with colorectal tumour cells. Of the T cells that proliferated upon incubation

with TAMs, 71% expressed PI3K inhibitor CD25, an activation marker, and 62% produced IFN-γ, a type-1 inflammatory cytokine (Fig. 4C), indicating that TAMs were able to activate type-1 T cells. There was no activation of type-2, type-17 or regulatory-T cells, indicated by the lack of IL-4, IL-17A or FoxP3 (Fig. 4C and D). Together, these results illustrated that TAMs in the colorectal cancer model were capable of stimulating T-cell proliferation and promoting type-1 PIK3C2G T-cell responses. To confirm the in vitro findings on colorectal TAMs, we studied primary tumour tissues from five colorectal cancer patients (Table 1). Pro-inflammatory TAMs were detected in the colorectal tumour sections, as they stained positive for IFN-γ (Fig. 5A, white arrows). The percentage of TAMs that were IFN-γ+ in each tumour sample was quantified using the software TissueQuest, on five images (each ∼350×250 μm) randomly taken from each tumour tissue section. The images

were analysed together to give a representative plot for every tumour sample (Supporting Information Fig. 7). This approach takes into account variations from different parts of the tissue section. The percentage of macrophages that were IFN-γ+ in the tumour samples varied from 6.6 to 50% (Fig. 5B and Table 1). To confirm the in vitro findings that TAMs in colorectal cancers could attract T cells, we quantified the numbers of tumour-infiltrating T cells and TAMs. Indeed, the numbers of tumour-infiltrating T cells and TAMs were highly correlated (r2=0.66, Fig. 5C). Furthermore, the TAMs and T cells were often observed to be in close contact (Fig. 5D, black arrows), suggesting direct interaction of the two cell types, such as antigen presentation to and co-stimulation of T cells by TAMs.

These results could indicate that healthy aging involves arterial remodeling, such as increased brachial diameter [16,18,66], thereby providing a compensatory mechanism for the impairment of NO• signaling. Similar observations MLN2238 mouse have been shown using the skin blood flow model [34]. Although NO•-dependent cutaneous vasodilation was impaired in the elderly, there was no significant difference in the reflex cutaneous vasodilation threshold between old and young subjects [34]. Unfortunately, due to the relative nature of Laser-Doppler probes, cutaneous raw blood flow cannot be used to assess age-related

structural changes. l-Arginine supplementation and arginase inhibition improve thermoregulatory cutaneous vasodilation in the elderly, confirming the NO•-dependency of this age-related alteration in vascular selleck chemicals reactivity

[35]. Although the aforementioned studies suggest that NO• availability is impaired in the elderly, a recent study [21] has shown that cellular signaling downstream of NO•, i.e., activation of cAMP and cGMP, is preserved in smooth muscle cells of older subjects. Therefore, we could speculate that NO• production is blunted in the elderly, whereas NO• bioavailability is not decreased. Vascular structural changes observed in the elderly [16,18,66] may also impact NO•-dependent vasodilation. Increased basal and submaximal blood flow through larger vessels may compensate for impaired reactivity and a decrease in the shear stress-induced endothelial NO• production. This “new” healthy vascular status in the elderly could be

associated with a new endothelial redox status in which NO• production is not the primary determinant of endothelium-dependent-vasodilation. Although some reports describe H2O2 as an EDHF in humans [53,58], others have offered conflicting evidence regarding the role of H2O2 in mediating endothelium-dependent vasodilation [12,30,32,44,53,57,62,69]. Hamilton et al. [30] reported that NO•/prostanoid-independent relaxation of human radial arteries to carbachol was resistant to treatment with either SOD or catalase, suggesting that this EDHF-like component of the endothelium-dependent response to carbachol was not mediated by H2O2. Meloxicam It is important to note that these authors assessed only the contribution of H2O2 that originated from O2•−. In contrast, Nacitarhan et al. [62] studied internal thoracic artery rings and found that authentic H2O2 produced dose-dependent relaxations that were blunted by 4-aminopyridine, a voltage-dependent potassium channel blocker. These contradictory results may reflect differences in the vascular beds and vasodilatory stimuli being studied. Using a similar approach, Conklin et al. [12] assessed vasoreactivity to H2O2 in rings from human radial arteries, internal mammary arteries, and saphenous veins.

In tuberculosis patients, IL-1β is expressed in excess [15] at the site of the disease [16]. IL1 β +3954 C to T (rs1143634) has been associated with periodontitis [17] and tuberculosis [18]. IL-10 a Th2 cytokine gene mapped to chromosome 1 is a potent inhibitor of T cell function, major histocompatibility complex (MHC) class II expression, antigen specific proliferation and IFN-γ synthesis [19]. Interindividual variations in

IL-10 production are genetically contributed by polymorphisms within the IL-10 promoter (rs1800896) [20]. The polymorphism at position -1082 may affect the binding of this transcriptional factor and therefore alter transcriptional selleck chemical activation [21]. The aim of this study was to determine the association of IL-1β +3954 C/T and IL-10-1082 G/A gene polymorphisms susceptible to tuberculosis in patients and their household contacts. A total of 300 subjects were included in the study

which consists of tuberculosis patients, their household contacts learn more (HHC) and age–sex-matched healthy controls (HC) of 100 each group. Patients who attended free chest clinic at Mahavir Hospital (PPM-DOTS) were recruited based on radiographic examination, sputum culture for acid-fast bacilli (AFB) and histocytological examination. Tuberculin skin test (TST) positivity was assessed both in patients and household contacts by administering 5 tuberculin Cyclin-dependent kinase 3 units (TU) intradermally on the volar surface of the left arm. An induration of >10 mm within 48–72 h was considered positive (TST+). In healthy controls, TST was not performed. Body Mass Index (BMI) was calculated in all the subjects. The study was approved by the Institutional Ethics Committee, and written informed consent was obtained from each participant. Genomic DNA was extracted from venous

blood (1–2 ml) using DNA isolation kit (Flexi gene DNA isolation kit) according to the manufacturer’s protocol. Quantity and quality of DNA was confirmed by spectrophotometer (Thermo scientific), and DNA was stored at −20 °C. The IL-1β +3954 C/T was genotyped by restriction fragment length polymorphism (RFLP) where a 249-bp fragment of the IL-1β exon 5 was amplified using forward primer 5′-gtt gtc atc aga ctt tga cc-3′ and reverse primer 5′-ttc agt tca tat gga cca ga-3′ in a 20μl reaction. The mixture was amplified for three cycles of 95 °C for 4 min, then 30 cycles of 95 °C for 30 s, 59 °C for 30 s, 72 °C for 30 s and then a final 4 min at 72 °C. The products were digested overnight at 65 °C with 2.5 U Taq 1 and run on a 2% agarose gel, generating the following patterns: single band of 249 bp, TT homozygote; two bands at 135 and 114 bp, CC homozygote; all three bands, CT heterozygote (Fig. 1A). IL-10-1082 G/A polymorphism was genotyped by amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method.

29 These proteins, which belong to the bZIP group Protein Tyrosine Kinase inhibitor of DNA-binding proteins, have leucine zippers through which they associate

to form a variety of homo- and hetero-dimers that bind to common AP-1 sites (TRE-TGAC/GTCA) or (CRE-TGACTCA) in DNA.30 Both ATF (ATF2, ATF3, B-ATF, JDP1, JDP2) and Maf (c-MAF, MafA, MafB, Nr1) are also considered members of this family based on their dimerization potential with Fos or Jun.29 Jun-proteins, but not Fos-proteins, are known to undergo homo-dimerization.31 Hetero-dimerization of Fos with Jun is crucial for nuclear-cytoplasmic shuttling.32 Monomeric Fos and Jun shuttle actively but hetero-dimerization of both proteins inhibits their cytoplasmic shuttling. Surprisingly, this retro-transport inhibition is not caused by the binding of the AP-1 complex to DNA.32 Levels of Fos and Jun proteins in T cells are either low or absent and are generally induced on signalling.33,34 Activity of AP-1 is regulated by mitogen-activated protein kinases (MAPK).35,36 Extra-cellular signal-regulated kinase (ERK) activation causes c-Fos induction, which results in increased synthesis of c-Fos and translocation to the nucleus. VX 809 In the nucleus it combines with pre-existing Jun proteins to form AP-1 dimers that are more stable than those formed by Jun proteins alone.30 It has been shown that ERK-1 is associated with the

synapse after TCR stimulation and prevents docking of Src homology-2 (SH2) domain-containing phosphatase -1 (SHP-1) phospha-tase.37–39 Transcription of c-Fos is regulated by ternary complex factors (Elk-1, SAP-1 and SAP-2) of which Elk-1 is phosphorylated by ERK.30,40 The c-Jun is expressed at low levels in unstimulated cells and its promoter is constitutively occupied by Jun-activating transcription factor 2 (ATF2) dimer.41,42 Phosphorylation of c-Jun by Jun N-terminal kinases (JNKs) and of ATF2 by JNKs or p38MAPK stimulates their ability to activate transcription, thereby leading to c-Jun induction.30 As part of their negative

regulation, AP-1 proteins are degraded in both ubiquitin-dependent and ubiquitin-independent manners.43–45 The GSK-3 can inhibit AP-1 transcriptional activity by producing inhibitory phosphorylation on Jun.12,46 The MAPK are negatively regulated by MAPK phosphatases, which are known to interact with the cytoplasmic tail of CD28 and are regulated by CD28 signalling.47,48 Mice OSBPL9 lacking c-Jun die at mid-gestation, indicating that it is an essential factor required for development.49 Mice lacking c-Fos are growth retarded and develop osteoporosis with a reduced number of B cells.50,51 The function of peripheral T cells (including proliferation and production of cytokines), however, is not impaired in c-Fos knockout mice.52 This lack of impairment could be the result of degeneracy among Fos members. In T cells, AP-1 contributes significantly to the regulation of the IL-2 gene.53 The main transcriptional partners of AP-1 are NFAT proteins.

Imaeda et al.

demonstrated that the mortality associated with acetaminophen-induced hepatotoxicity was partially dependent on NLRP3 38. Mice deficient in components of the NLRP3 inflammasome were protected from the lethal effects of RO4929097 cell line acetaminophen-induced hepatotoxicity in vivo and had reduced liver injury compared to WT mice. Although not directly examined in this study, it is likely that acetaminophen-induced necrosis of hepatocytes, similar to necrosis induced by pressure-disruption and complement, activates the NLRP3 inflammasome in macrophages that encounter these necrotic cells with resultant activation of caspase-1 and processing and secretion of IL-1β. Interestingly, DNA released from damaged hepatocytes was found to stimulate the production of pro-IL-1β and pro-IL-18 through LEE011 manufacturer stimulation of TLR9 38. This raises the possibility that cytosolic nucleic acid sensors such as RIG-I and AIM2 may also play a role in sterile inflammatory responses to necrotic cell death. In addition, NLRP3 has also been shown to be activated in response to cytoplasmic DNA 39, which may also play a role in NLRP3 inflammasome activation in response to acetaminophen-induced hepatotoxicity. Tumor cell death induced

by certain chemotherapeutic agents such as anthracyclines and oxaliplatin elicit an immunogenic response that is required for tumor eradication. Ghiringhelli et al. found that oxaliplatin-treated tumor cells were capable of activating the NLRP3 inflammasome in dendritic cells resulting in the secretion of IL-1β 37. Importantly, the priming of IFN-γ-producing CD8+ T cells by dying tumor cells was also dependent on the NLRP3 inflammasome. The importance of NLRP3 in mediating the adjuvant

effects of alum and uric acid has parallels to these new findings that necrotic cells mediate their immunogenicity through NLRP3. Ghiringhelli et al. also found that tumors established Ergoloid in mice deficient in components of the NLRP3-inflammasome had poorer responses to oxaliplatin compared with WT mice 37. Both Iyer et al. and Ghiringhelli et al. demonstrated that ATP released from the necrotic cells was responsible for activation of the NLRP3 inflammasome via the P2X7 receptor 22, 37. Importantly, uric acid, another DAMP that has been postulated to play a role in responses to necrotic cells, was not involved in the ability for necrotic cells to activate the NLRP3 inflammasome. The half-life of extracellular ATP is brief due to efficient degradation by ectoenzymes. Hence, preformed ATP released from the dying cell is likely sensed in close proximity to the necrotic insult. Additionally, we found actively respiring mitochondria released from necrotic cells generate ATP that activates the NLRP3 inflammasome, and also allows the ATP to be carried further from the site of initial insult 22 (Fig. 2).

Since neutrophils are prevalent among infiltrates and are effective IL-17 producers, as reported in this report and others [36, 37], and are strongly recruited by

IL-17, the positive feedback loop is likely initiated by chemokine-producing resident corneal cells. This attribute explains the rapid fungal growth in immunocompetent BALB/c mice. In the corneas of nude mice, however, the lack of chemokine production leads to decreased leukocyte infiltration, which in turn hampers fungal expansion in the cornea. Our survey of chemokine expression in inoculated corneas confirmed that nude mice are deficient BGJ398 mouse in overall chemokine production (Fig. 6D and E). Furthermore, the CXCL2 supplementation experiments in both nude and BALB/c mice (Fig. 7) provided further support for this hypothesis. Since both APCs in the stroma [9, 10] and corneal epithelial cells as well as

mTOR inhibitor keratinocytes [38-40] are the potential resources of such cytokine/chemokines, the exact mechanisms accounting for the decreased ability of nude mice corneas to produce chemokines and IL-6 (e.g. one of the Th17-inducing factors) upon fungal challenge deserve further investigation. Another apparent issue is that immunodeficient nude mice or CD4+ T-cell-depleted mice did not develop CaK while previous reports have shown that HIV/AIDS patients are more likely to develop FK [14-16]. This might occur because HIV infections deplete CD4+ T cells gradually and partially. Nevertheless, the FK model employs a large pathogen load directly injected into stroma of CD4-null mice. The differences in antimicrobial mechanisms between humans and mice might reconcile pheromone the above inconsistency. Notably, the immunocompetent mice in this study were able to recover from CaK in 3 weeks without treatment, but untreated human patients with FK usually lose corneal function soon after symptoms emerge. Thus, more studies are

required to determine whether IL-17 activity in murine CaK is conserved in FK in humans, including HIV carriers. Given the well-established fact that Th17 cells are a major source of IL-17, and our results showing that CD4-deficient mice did not develop CaK, it is tempting to speculate that IL-17 and Th17 cells functionally converge in the CaK formation pathway. However, based on the difference in the number of CD4+ T cells and neutrophils in BALB/c corneas with CaK (Fig. 5), together with the fact that exogenous CXCL2 reconstituted sensitivity of nude mice to CaK (Fig. 7), we hypothesize that CaK development is neutrophil dependent, especially in the early phase of infection. This neutrophil-dominated response might occur with Th17 cells, as in BALB/c mice, or independent of Th17 cells, as in CXCL2-sensitized nude mice. Similar to our study, Karthikeyan et al.

2. The reaction was initiated by adding 50 μL of 2 mM N-carboxybenzoxy-L-lysine thiobenzyl ester (Sigma). After 30 min, absorbance was measured at 420 nm on an ELISA plate reader. We transfected Vγ9Vδ2 T cells with various amounts of a pool of four control or NKG2D siRNAs (4, 40, 80 pmol) using an Amaxa nucleofector apparatus (Amaxa Biosystems), as described by the manufacturer. Purified monocytes were seeded into 48-well plates at a density of 0.7×106/mL

in complete culture BMS-777607 clinical trial medium (RPMI+10% FCS) and differentiated into macrophages by a treatment of 6 days with recombinant human M-CSF (10 ng/mL). Macrophages were infected with Brucella suis 1330 at a MOI of 30. After 1 h, the cells were washed twice with PBS, gentamicin was added to kill non-phagocytosed bacteria and then macrophages were incubated as indicated alone, with control or siRNA-transfected Vγ9Vδ2 T cells in the presence of different blocking Abs (anti-NKG2D mAb (M585, 10 μg/mL), anti-ULBP1 mAb (10 μg/mL). The ratio Vγ9Vδ2 T cells/macrophages used in the infection experiments was (1.5/1) and Vγ9Vδ2 T cells were activated by the addition of 0.5 nM

HMB-PP. At various post-infection times (2, 24 and 48 h), intracellular bacteria development was estimated by lysing the infected macrophages with 0.1% Triton X-100. Serial dilutions of lysates were plated on tryptic soy broth agar plates and CFUs were counted. The mean of triplicate samples is shown for each Depsipeptide price data point with its SD and is representative of a minimum of three experiments performed on separate human

blood donors. p-Value was calculated Small molecule library by using an un-paired Student’s t test where a difference was considered to be significant when p<0.05. We would like to thank AMGEN for providing ULBP-LZ fusion proteins and anti-NKG2D mAbs (M585 and M580). This work was supported by institutional grants from CNRS. Conflict of interest: The authors declare no financial or commercial conflict of interest. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. "
“Adipose tissue is a dynamic organ that makes up a substantial proportion of the body; in severe obesity it can account for 50% of body mass. Details of the unique immune system resident in human and murine adipose tissue are only recently emerging, and so it has remained a largely unexplored and unappreciated immune site until now. Adipose tissue harbours a unique collection of immune cells, which often display unusual functions compared with their counterparts elsewhere in the body. These resident immune cells are key to maintaining tissue and immune homeostasis, yet in obesity their chronic aberrant stimulation can contribute to the inflammation and pathogenesis associated with obesity.