Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization.

The signals driving the adaptation of type 2 dendritic cells (DC2s) to diverse peripheral environments remain mostly undefined. We show that differentiation of CD11blo migratory DC2s-a DC2 population unique to the dermis-required IL-13 signaling dependent on the transcription factors STAT6 and KLF4, whereas DC2s in lung and small intestine were STAT6-independent. Similarly, human DC2s in skin expressed an IL-4 and IL-13 gene signature that was not found in blood, spleen and lung DCs. In mice, IL-13 was secreted homeostatically by dermal innate lymphoid cells and was independent of microbiota, TSLP or IL-33. In the absence of IL-13 signaling, dermal DC2s were stable in number but remained CD11bhi and showed defective activation in response to allergens, with diminished ability to support the development of IL-4+GATA3+ helper T cells (TH), whereas antifungal IL-17+RORγt+ TH cells were increased. Therefore, homeostatic IL-13 fosters a noninflammatory skin environment that supports allergic sensitization.

Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection.

The phenotypic and functional dichotomy between IRF8+ type 1 and IRF4+ type 2 conventional dendritic cells (cDC1s and cDC2s, respectively) is well accepted; it is unknown how robust this dichotomy is under inflammatory conditions, when additionally monocyte-derived cells (MCs) become competent antigen-presenting cells (APCs). Using single-cell technologies in models of respiratory viral infection, we found that lung cDC2s acquired expression of the Fc receptor CD64 shared with MCs and of IRF8 shared with cDC1s. These inflammatory cDC2s (inf-cDC2s) were superior in inducing CD4+ T helper (Th) cell polarization while simultaneously presenting antigen to CD8+ T cells. When carefully separated from inf-cDC2s, MCs lacked APC function. Inf-cDC2s matured in response to cell-intrinsic Toll-like receptor and type 1 interferon receptor signaling, upregulated an IRF8-dependent maturation module, and acquired antigens via convalescent serum and Fc receptors. Because hybrid inf-cDC2s are easily confused with monocyte-derived cells, their existence could explain why APC functions have been attributed to MCs.

Tissue-specific antigen-presenting cells contribute to distinct phenotypes of allergy.

Antigen-presenting cells (APCs) are critical cells bridging innate and adaptive immune responses by taking up, processing, and presenting antigens to naïve T cells. At steady state, APCs thus control both tissue homeostasis and the induction of tolerance. In allergies however, APCs drive a Th2-biased immune response that is directed against otherwise harmless antigens from the environment. The main types of APCs involved in the induction of allergy are dendritic cells, monocytes, and macrophages. However, these cell types can be further divided into local, tissue-specific populations that differ in their phenotype, migratory capacity, T-cell activating potential, and production of effector molecules. Understanding if distinct populations of APCs contribute to either tissue-specific immune tolerance, allergen sensitization, or allergic inflammation will allow us to better understand disease pathology and develop targeted treatment options for different stages of allergic disease. Therefore, this review describes the main characteristics, phenotypes, and effector molecules of the APCs involved in the induction of allergen-specific Th2 responses in affected barrier sites, such as the skin, nose, lung, and gastrointestinal tract. Furthermore, we highlight open questions that remain to be addressed to fully understand the contribution of different APCs to allergic disease.

Mitochondrial translation requires folate-dependent tRNA methylation.

Folates enable the activation and transfer of one-carbon units for the biosynthesis of purines, thymidine and methionine. Antifolates are important immunosuppressive and anticancer agents. In proliferating lymphocytes and human cancers, mitochondrial folate enzymes are particularly strongly upregulated. This in part reflects the need for mitochondria to generate one-carbon units and export them to the cytosol for anabolic metabolism. The full range of uses of folate-bound one-carbon units in the mitochondrial compartment itself, however, has not been thoroughly explored. Here we show that loss of the catalytic activity of the mitochondrial folate enzyme serine hydroxymethyltransferase 2 (SHMT2), but not of other folate enzymes, leads to defective oxidative phosphorylation in human cells due to impaired mitochondrial translation. We find that SHMT2, presumably by generating mitochondrial 5,10-methylenetetrahydrofolate, provides methyl donors to produce the taurinomethyluridine base at the wobble position of select mitochondrial tRNAs. Mitochondrial ribosome profiling in SHMT2-knockout human cells reveals that the lack of this modified base causes defective translation, with preferential mitochondrial ribosome stalling at certain lysine (AAG) and leucine (UUG) codons. This results in the impaired expression of respiratory chain enzymes. Stalling at these specific codons also occurs in certain inborn errors of mitochondrial metabolism. Disruption of whole-cell folate metabolism, by either folate deficiency or antifolate treatment, also impairs the respiratory chain. In summary, mammalian mitochondria use folate-bound one-carbon units to methylate tRNA, and this modification is required for mitochondrial translation and thus oxidative phosphorylation.

Outcome After Reconstruction of 43 Digital Nerve Defects With Muscle-in-Vein Conduits.

PURPOSE: Muscle-in-vein conduits provide an alternative for bridging digital nerve defects when tension-free suture is not possible. Low donor site morbidity and absence of additional costs are favorable advantages compared with autografts or conduits. METHODS: We retrospectively reviewed 37 patients with 43 defects of proper palmar digital nerves. Primary repair by muscle-in-vein conduits was performed in 22 cases, whereas 21 cases underwent secondary reconstruction. Recovery of sensibility was assessed using static and moving 2-point discrimination and Semmes-Weinstein monofilament testing. Results were compared with the contralateral side serving as a control. Outcome data were stratified according to international guidelines and evaluated for differences in terms of age, gap length, time of reconstruction, and concomitant injuries. RESULTS: The median gap length was 20 mm (range, 9-60 mm). After a median follow-up of 25.0 months (interquartile range, 29.0 months), the median static and moving 2-point discrimination were 7.0 mm and 5.0 mm (interquartile range, 3.0 mm), respectively. The evaluation with Semmes-Weinstein monofilament revealed a median reduction of sensibility of 2 levels compared with the contralateral side. According to the American Society for Surgery of the Hand guidelines, 81.4% of the results were classified as excellent or good, whereas fair and poor results were noted in 9.3% of the cases each. The modified Highet and Sander's criteria rated complete clinical recovery in 13 cases; 23 results were regarded as S3+. CONCLUSIONS: Muscle-in-vein conduits can be considered for primary and secondary reconstruction of digital nerves. Successful sensory recovery in terms of measurable 2-point discrimination was achieved in 91% of all cases. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

General Population and Surgeon Preferences for Pollicization Versus Toe-To-Thumb Transfer for Reconstruction of Traumatic Thumb Loss in Adults: An International, Multi-Center Survey Study.

PURPOSE: Data objectively comparing outcomes following pollicization versus toe-to-thumb transfer for reconstruction after traumatic thumb amputation in adults remains sparse. Given that this decision is reliant on personal preference, it is important to understand the subjective nature of these preferences, particularly in the context of culture. The purpose of this study was to compare Eastern and Western societal and hand surgeon preferences for pollicization versus toe-to-thumb transfer for traumatic thumb reconstruction. METHODS: Investigators from 6 international locations recruited local hand surgeons and members of the general population. Austria, Germany, the United States, and Spain were grouped as "Western" nations. China and India separately represented "Eastern" nations. Participants completed a questionnaire evaluating their personal preferences for pollicization and toe-to-thumb transfer. The questions posed to the general population and hand surgeons were identical. Demographic data were also collected. RESULTS: When comparing the Western nations, China, and India, there was no difference in personal preferences within the general population for pollicization versus toe-to-thumb transfer. In contrast, most Indian hand surgeons favored toe-to-thumb transfer and most Western surgeons were uncertain about which procedure they would favor. Surgeons had more optimistic expectations regarding postoperative hand function, new thumb sensation, and hand appearance following pollicization than the general population. Similarly, for toe-to-thumb transfer, a greater proportion of surgeons predicted good-to-excellent function, sensation, and appearance. CONCLUSIONS: There was no clear, observed "East" versus "West" difference in the general population's personal preferences for pollicization versus toe-to-thumb transfer among study participants. The members of the general population and hand surgeons had different outcome expectations. CLINICAL RELEVANCE: Understanding how culture influences patient and hand surgeon preferences for pollicization versus toe-to-thumb transfer may help guide future decision-making for traumatic thumb reconstruction.

S1 Guideline onychomycosis.

Onychomycosis is a fungal infection of the fingernails and toenails. In Europe, tinea unguium is mainly caused by dermatophytes. The diagnostic workup comprises microscopic examination, culture and/or molecular testing (nail scrapings). Local treatment with antifungal nail polish is recommended for mild or moderate nail infections. In case of moderate to severe onychomycosis, oral treatment is recommended (in the absence of contraindications). Treatment should consist of topical and systemic agents. The aim of this update of the German S1 guideline is to simplify the selection and implementation of appropriate diagnostics and treatment. The guideline was based on current international guidelines and the results of a literature review conducted by the experts of the guideline committee. This multidisciplinary committee consisted of representatives from the German Society of Dermatology (DDG), the German-Speaking Mycological Society (DMykG), the Association of German Dermatologists (BVDD), the German Society for Hygiene and Microbiology (DGHM), the German Society of Pediatric and Adolescent Medicine (DGKJ), the Working Group for Pediatric Dermatology (APD) and the German Society for Pediatric Infectious Diseases (DGPI). The Division of Evidence-based Medicine (dEBM) provided methodological assistance. The guideline was approved by the participating medical societies following a comprehensive internal and external review.

Cardio-respiratory motion-corrected 3D cardiac water-fat MRI using model-based image reconstruction.

PURPOSE: Myocardial fat infiltrations are associated with a range of cardiomyopathies. The purpose of this study was to perform cardio-respiratory motion-correction for model-based water-fat separation to image fatty infiltrations of the heart in a free-breathing, non-cardiac-triggered high-resolution 3D MRI acquisition. METHODS: Data were acquired in nine patients using a free-breathing, non-cardiac-triggered high-resolution 3D Dixon gradient-echo sequence and radial phase encoding trajectory. Motion correction was combined with a model-based water-fat reconstruction approach. Respiratory and cardiac motion models were estimated using a dual-mode registration algorithm incorporating both motion-resolved water and fat information. Qualitative comparisons of fat structures were made between 2D clinical routine reference scans and reformatted 3D motion-corrected images. To evaluate the effect of motion correction the local sharpness of epicardial fat structures was analyzed for motion-averaged and motion-corrected fat images. RESULTS: The reformatted 3D motion-corrected reconstructions yielded qualitatively comparable fat structures and fat structure sharpness in the heart as the standard 2D breath-hold. Respiratory motion correction improved the local sharpness on average by 32% ± 24% with maximum improvements of 81% and cardiac motion correction increased the sharpness further by another 15% ± 11% with maximum increases of 31%. One patient showed a fat infiltration in the myocardium and cardio-respiratory motion correction was able to improve its visualization in 3D. CONCLUSION: The 3D water-fat separated cardiac images were acquired during free-breathing and in a clinically feasible and predictable scan time. Compared to a motion-averaged reconstruction an increase in sharpness of fat structures by 51% ± 27% using the presented motion correction approach was observed for nine patients.

Motion-compensated fat-water imaging for 3D cardiac MRI at ultra-high fields.

PURPOSE: Respiratory motion-compensated (MC) 3D cardiac fat-water imaging at 7T. METHODS: Free-breathing bipolar 3D triple-echo gradient-recalled-echo (GRE) data with radial phase-encoding (RPE) trajectory were acquired in 11 healthy volunteers (7M\4F, 21-35 years, mean: 30 years) with a wide range of body mass index (BMI; 19.9-34.0 kg/m2 ) and volunteer tailored B1+ shimming. The bipolar-corrected triple-echo GRE-RPE data were binned into different respiratory phases (self-navigation) and were used for the estimation of non-rigid motion vector fields (MF) and respiratory resolved (RR) maps of the main magnetic field deviations (ΔB0 ). RR ΔB0 maps and MC ΔB0 maps were compared to a reference respiratory phase to assess respiration-induced changes. Subsequently, cardiac binned fat-water images were obtained using a model-based, respiratory motion-corrected image reconstruction. RESULTS: The 3D cardiac fat-water imaging at 7T was successfully demonstrated. Local respiration-induced frequency shifts in MC ΔB0 maps are small compared to the chemical shifts used in the multi-peak model. Compared to the reference exhale ΔB0 map these changes are in the order of 10 Hz on average. Cardiac binned MC fat-water reconstruction reduced respiration induced blurring in the fat-water images, and flow artifacts are reduced in the end-diastolic fat-water separated images. CONCLUSION: This work demonstrates the feasibility of 3D fat-water imaging at UHF for the entire human heart despite spatial and temporal B1+ and B0 variations, as well as respiratory and cardiac motion.

CRISPR/Cas9-mediated genome editing of Schistosoma mansoni acetylcholinesterase.

CRISPR/Cas9-mediated genome editing shows cogent potential for the genetic modification of helminth parasites. We report successful gene knock-in (KI) into the genome of the egg of Schistosoma mansoni by combining CRISPR/Cas9 with single-stranded oligodeoxynucleotides (ssODNs). We edited the acetylcholinesterase (AChE) gene of S. mansoni targeting two guide RNAs (gRNAs), X5 and X7, located on exon 5 and exon 7 of Smp_154600, respectively. Eggs recovered from livers of experimentally infected mice were transfected by electroporation with a CRISPR/Cas9-vector encoding gRNA X5 or X7 combining with/ without a ssODN donor. Next generation sequencing analysis of reads of amplicon libraries spanning targeted regions revealed that the major modifications induced by CRISPR/Cas9 in the eggs were generated by homology directed repair (HDR). Furthermore, soluble egg antigen from AChE-edited eggs exhibited markedly reduced AChE activity, indicative that programed Cas9 cleavage mutated the AChE gene. Following injection of AChE-edited schistosome eggs into the tail veins of mice, an significantly enhanced Th2 response involving IL-4, -5, -10, and-13 was detected in lung cells and splenocytes in mice injected with X5-KI eggs in comparison to control mice injected with unmutated eggs. A Th2-predominant response, with increased levels of IL-4, -13, and GATA3, also was induced by X5 KI eggs in small intestine-draining mesenteric lymph node cells when the gene-edited eggs were introduced into the subserosa of the ileum of the mice. These findings confirmed the potential and the utility of CRISPR/Cas9-mediated genome editing for functional genomics in schistosomes.

3D Free-breathing multichannel absolute B1+ Mapping in the human body at 7T.

PURPOSE: To introduce and investigate a method for free-breathing three-dimensional (3D) B1+ mapping of the human body at ultrahigh field (UHF), which can be used to generate homogenous flip angle (FA) distributions in the human body at UHF. METHODS: A 3D relative B1+ mapping sequence with a radial phase-encoding (RPE) k-space trajectory was developed and applied in 11 healthy subjects at 7T. An RPE-based actual flip angle mapping method was applied with a dedicated B1+ shim setting to calibrate the relative B1+ maps yielding absolute B1+ maps of the individual transmit channels. The method was evaluated in a motion phantom and by multidimensional in vivo measurements. Additionally, 3D gradient echo scans with and without static phase-only B1+ shims were used to qualitatively validate B1+ shim predictions. RESULTS: The phantom validation revealed good agreement for B1+ maps between dynamic measurement and static reference acquisition. The proposed 3D method was successfully validated in vivo by comparing magnitude and phase distributions with a 2D Cartesian reference. 3D B1+ maps free from visible motion artifacts were successfully acquired for 11 subjects with body mass indexes ranging from 19 kg/m2 to 34 kg/m2 . 3D respiration-resolved absolute B1+ maps indicated FA differences between inhalation and exhalation up to 15% for one channel and up to 24% for combined channels for shallow breathing. CONCLUSION: The proposed method provides respiration-resolved absolute 3D B1+ maps of the human body at UHF, which enables the investigation and development of 3D B1+ shimming and parallel transmission methods to further enhance body imaging at UHF.

MR1-dependent immune surveillance of the skin contributes to pathogenesis and is a photobiological target of UV light therapy in a mouse model of atopic dermatitis.

BACKGROUND: Mucosal-associated invariant T (MAIT) cells are unconventional T cells which recognize microbial metabolites presented by the major histocompatibility complex class I-related molecule MR1. Although MAIT cells have been shown to reside in human and murine skin, their contribution to atopic dermatitis (AD), an inflammatory skin disease associated with barrier dysfunction and microbial translocation, has not yet been determined. METHODS: Genetic deletion of MR1 and topical treatment with inhibitory MR1 ligands, which result in the absence and functional inhibition of MAIT cells, respectively, were used to investigate the role of MR1-dependent immune surveillance in a MC903-driven murine model of AD. RESULTS: The absence or inhibition of MR1 arrested AD disease progression through the blockade of both eosinophil activation and recruitment of IL-4- and IL-13-producing cells. In addition, the therapeutic efficacy of phototherapy against MC903-driven AD could be increased with prior application of folate, which photodegrades into the inhibitory MR1 ligand 6-formylpterin. CONCLUSION: We identified MAIT cells as sentinels and mediators of cutaneous type 2 immunity. Their pathogenic activity can be inhibited by topical application or endogenous generation, via phototherapy, of inhibitory MR1 ligands.

Imaging coronary plaques using 3D motion-compensated [18F]NaF PET/MR.

BACKGROUND: Cardiac PET has recently found novel applications in coronary atherosclerosis imaging using [18F]NaF as a radiotracer, highlighting vulnerable plaques. However, the resulting uptakes are relatively small, and cardiac motion and respiration-induced movement of the heart can impair the reconstructed images due to motion blurring and attenuation correction mismatches. This study aimed to apply an MR-based motion compensation framework to [18F]NaF data yielding high-resolution motion-compensated PET and MR images. METHODS: Free-breathing 3-dimensional Dixon MR data were acquired, retrospectively binned into multiple respiratory and cardiac motion states, and split into fat and water fraction using a model-based reconstruction framework. From the dynamic MR reconstructions, both a non-rigid cardiorespiratory motion model and a motion-resolved attenuation map were generated and applied to the PET data to improve image quality. The approach was tested in 10 patients and focal tracer hotspots were evaluated concerning their target-to-background ratio, contrast-to-background ratio, and their diameter. RESULTS: MR-based motion models were successfully applied to compensate for physiological motion in both PET and MR. Target-to-background ratios of identified plaques improved by 7 ± 7%, contrast-to-background ratios by 26 ± 38%, and the plaque diameter decreased by -22 ± 18%. MR-based dynamic attenuation correction strongly reduced attenuation correction artefacts and was not affected by stent-related signal voids in the underlying MR reconstructions. CONCLUSIONS: The MR-based motion correction framework presented here can improve the target-to-background, contrast-to-background, and width of focal tracer hotspots in the coronary system. The dynamic attenuation correction could effectively mitigate the risk of attenuation correction artefacts in the coronaries at the lung-soft tissue boundary. In combination, this could enable a more reproducible and reliable plaque localisation.

Evaluation of synergistic image registration for motion-corrected coronary NaF-PET-MR.

Coronary artery disease (CAD) is caused by the formation of plaques in the coronary arteries and is one of the most common cardiovascular diseases. NaF-PET can be used to assess plaque composition, which could be important for therapy planning. One of the main challenges of NaF-PET is cardiac and respiratory motion which can strongly impair diagnostic accuracy. In this study, we investigated the use of a synergistic image registration approach which combined motion-resolved MR and PET data to estimate cardiac and respiratory motion. This motion estimation could then be used to improve the NaF-PET image quality. The approach was evaluated with numerical simulations and in vivo scans of patients suffering from CAD. In numerical simulations, it was shown, that combining MR and PET information can improve the accuracy of motion estimation by more than 15%. For the in vivo scans, the synergistic image registration led to an improvement in uptake visualization. This is the first study to assess the benefit of combining MR and NaF-PET for cardiac and respiratory motion estimation. Further patient evaluation is required to fully evaluate the potential of this approach. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 1'.

Motion estimation and correction for simultaneous PET/MR using SIRF and CIL.

SIRF is a powerful PET/MR image reconstruction research tool for processing data and developing new algorithms. In this research, new developments to SIRF are presented, with focus on motion estimation and correction. SIRF's recent inclusion of the adjoint of the resampling operator allows gradient propagation through resampling, enabling the MCIR technique. Another enhancement enabled registering and resampling of complex images, suitable for MRI. Furthermore, SIRF's integration with the optimization library CIL enables the use of novel algorithms. Finally, SPM is now supported, in addition to NiftyReg, for registration. Results of MR and PET MCIR reconstructions are presented, using FISTA and PDHG, respectively. These demonstrate the advantages of incorporating motion correction and variational and structural priors. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 2'.

Influence of cleaning methods after 3D printing on two-body wear and fracture load of resin-based temporary crown and bridge material.

OBJECTIVES: To investigate the impact of different cleaning methods on the fracture load and two-body wear of additively manufactured three-unit fixed dental prostheses (FDP) for long-term temporary use, compared to the respective outcomes of milled provisional PMMA FDPs. MATERIALS AND METHODS: Shape congruent three-unit FDPs were 3D printed using three different resin-based materials [FPT, GCT, NMF] or milled [TEL] (N = 48, n = 16 per group). After printing, the FDPs were cleaned using: Isopropanol (ISO), Yellow Magic 7 (YEL), or centrifugal force (CEN). Chewing simulation was carried out with a vertical load of 50 N (480,000 × 5 °C/55 °C). Two-body wear and fracture load were measured. Data were analyzed using global univariate ANOVA with partial eta squared, Kruskal-Wallis H, Mann-Whitney U, and Spearman's rho test (p < 0.05). RESULTS: TEL showed less wear resistance than FPT (p = 0.001) for all cleaning methods tested. Concerning vertical material loss, NMF and GCT were in the same range of value (p = 0.419-0.997), except within FDPs cleaned in ISO (p = 0.021). FPT showed no impact of cleaning method on wear resistance (p = 0.219-0.692). TEL (p < 0.001) showed the highest and FPT (p < 0.001) the lowest fracture load. Regarding the cleaning methods, specimens treated with ISO showed lower fracture load than specimens cleaned with CEN (p = 0.044) or YEL (p = 0.036). CONCLUSIONS: The material selection and the cleaning method can have an impact on two-body wear and fracture load results. CLINICAL RELEVANCE: Printed restorations showed superior two-body wear resistance compared to milled FDPs but lower fracture load values. Regarding cleaning methods, ISO showed a negative effect on fracture load compared to the other methods tested.

Cutaneous nerve fields of the anteromedial lower limb-Determination with selective ultrasound-guided nerve blockade.

BACKGROUND: This study aimed to determine the peripheral cutaneous nerve fields (CNF), their variability, and potential overlap by selectively blocking the intermediate (IFCN) and medial (MFCN) femoral cutaneous nerves and the infrapatellar branch of the saphenous nerve (IPBSN) in healthy volunteers. METHODS: In this prospective study, ultrasound-guided nerve blockades of the IFCN, MFCN, and IPBSN in 14 healthy volunteers were administered. High-frequency probes (15-22 MHz) and 1 ml of 1% lidocaine per nerve were used. The area of sensory loss was determined using a pinprick, and all fields were drawn on volunteers' skin. A three-dimensional (3D) scan of all lower limbs was obtained and the three CNF and their potential overlap were measured. RESULTS: The mean size of innervation areas showed a high variability of peripheral CNF, with 258.58 ± 148.26 mm2 (95% CI, 169-348.18 mm2 ) for the IFCN, 193.26 ± 72.08 mm2 (95% CI, 124.45-262.08 mm2 ) for the MFCN, and 166.78 ± 121.30 mm2 (95% CI, 94.1-239.46 mm2 ) for the IPBSN. In 11 volunteers, we could evaluate an overlap between the IFCN and MFCN (range, 4.11-139.68 ± 42.70 mm2 ), and, in 10 volunteers, between the MFCN and IPBSN (range, 11.12-224.95 ± 79.61 mm2 ). In only three volunteers was an overlap area found between the IFCN and IPBSN (range, 7.46-224.95 ± 88.88 mm2 ). The 3D-scans confirmed the high variability of the peripheral CNF. CONCLUSIONS: Our study successfully determined CNF, their variability, and the overlap of the MFCN, IFCN, and IPBSN in healthy volunteers. Therefore, we encourage physicians to use selective nerve blockades to correctly determine peripheral CNF at the anteromedial lower limb.

Dendritic cells in Th2 immune responses and allergic sensitization.

Allergic responses are characterized by the activation of a specific subset of effector CD4+ T cells, the T-helper type 2 (Th2) cells, that respond to harmless environmental antigens causing inflammation and pathology. Th2 cells are also found in the context of parasite infections, where they can mediate parasite clearance and expulsion, and support tissue repair. The process that leads to the activation of Th2 cells in vivo is incompletely understood: while it has become clear that "conventional" dendritic cells are essential antigen-presenting cells for the initiation of Th2 immune responses, the molecules that are expressed by dendritic cells exposed to allergens, and the mediators that are produced as a consequence and signal to naïve CD4+ T cells to promote their development into effector Th2, remain to be defined. Here we summarize recent developments in the identification of the dendritic cell subsets involved in Th2 responses, review potential mechanisms proposed to explain the generation of these immune responses, and discuss the direct and indirect signals that condition dendritic cells to drive the development of Th2 responses during allergen or parasite exposure.

Autocalibrated cardiac tissue phase mapping with multiband imaging and k-t acceleration.

PURPOSE: To develop an autocalibrated multiband (MB) CAIPIRINHA acquisition scheme with in-plane k-t acceleration enabling multislice three-directional tissue phase mapping in one breath-hold. METHODS: A k-t undersampling scheme was integrated into a time-resolved electrocardiographic-triggered autocalibrated MB gradient-echo sequence. The sequence was used to acquire data on 4 healthy volunteers with MB factors of two (MB2) and three (MB3), which were reconstructed using a joint reconstruction algorithm that tackles both k-t and MB acceleration. Forward simulations of the imaging process were used to tune the reconstruction model hyperparameters. Direct comparisons between MB and single-band tissue phase-mapping measurements were performed. RESULTS: Simulations showed that the velocities could be accurately reproduced with MB2 k-t (average ± twice the SD of the RMS error of 0.08 ± 0.22 cm/s and velocity peak reduction of 1.03% ± 6.47% compared with fully sampled velocities), whereas acceptable results were obtained with MB3 k-t (RMS error of 0.13 ± 0.58 cm/s and peak reduction of 2.21% ± 13.45%). When applied to tissue phase-mapping data, the proposed technique allowed three-directional velocity encoding to be simultaneously acquired at two/three slices in a single breath-hold of 18 heartbeats. No statistically significant differences were detected between MB2/MB3 k-t and single-band k-t motion traces averaged over the myocardium. Regional differences were found, however, when using the American Heart Association model for segmentation. CONCLUSION: An autocalibrated MB k-t acquisition/reconstruction framework is presented that allows three-directional velocity encoding of the myocardial velocities at multiple slices in one breath-hold.