Dendritic cells (DCs) are crucial cells for initiating and maintaining immune response. They play critical role in homeostasis, inflammation, and autoimmunity. A number of molecules regulate their ...functions including synapse formation, migration, immunity, and induction of tolerance. A number of IEI are characterized by mutations in genes encoding several of these molecules resulting in immunodeficiency, inflammation, and autoimmunity in IEI. Currently, there are 465 Inborn errors of immunity (IEI) that have been grouped in 10 different categories. However, comprehensive studies of DCs have been reported in only few IEI. Here we have reviewed biology of DCs in IEI classified according to recently published IUIS classification. We have reviewed DCs in selected IEI in each group category and discussed in depth changes in DCs where significant data are available regarding role of DCs in clinical and immunological manifestations. These include severe immunodeficiency diseases, antibody deficiencies, combined immunodeficiency with associated and syndromic features, especially disorders of synapse formation, and disorders of immune regulation.
Dendritic cells (DCs) and monocytes are crucial mediators of innate and adaptive immune responses during viral infection, but misdirected responses by these cells may contribute to immunopathology. ...Here, we performed high-dimensional flow cytometry-analysis focusing on mononuclear phagocyte (MNP) lineages in SARS-CoV-2-infected patients with moderate and severe COVID-19. We provide a deep and comprehensive map of the MNP landscape in COVID-19. A redistribution of monocyte subsets toward intermediate monocytes and a general decrease in circulating DCs was observed in response to infection. Severe disease coincided with the appearance of monocytic myeloid-derived suppressor cell-like cells and a higher frequency of pre-DC2. Furthermore, phenotypic alterations in MNPs, and their late precursors, were cell-lineage-specific and associated either with the general response against SARS-CoV-2 or COVID-19 severity. This included an interferon-imprint in DC1s observed in all patients and a decreased expression of the coinhibitory molecule CD200R in pre-DCs, DC2s, and DC3 subsets of severely sick patients. Finally, unsupervised analysis revealed that the MNP profile, alone, pointed to a cluster of COVID-19 nonsurvivors. This study provides a reference for the MNP response to SARS-CoV-2 infection and unravels mononuclear phagocyte dysregulations associated with severe COVID-19.
Dendritic cells (DCs) are antigen-presenting cells controlling T cell activation. In humans, the diversity, ontogeny, and functional capabilities of DC subsets are not fully understood. Here, we ...identified circulating CD88−CD1c+CD163+ DCs (called DC3s) as immediate precursors of inflammatory CD88−CD14+CD1c+CD163+FcεRI+ DCs. DC3s develop via a specific pathway activated by GM-CSF, independent of cDC-restricted (CDP) and monocyte-restricted (cMoP) progenitors. Like classical DCs but unlike monocytes, DC3s drove activation of naive T cells. In vitro, DC3s displayed a distinctive ability to prime CD8+ T cells expressing a tissue homing signature and the epithelial homing alpha-E integrin (CD103) through transforming growth factor β (TGF-β) signaling. In vivo, DC3s infiltrated luminal breast cancer primary tumors, and DC3 infiltration correlated positively with CD8+CD103+CD69+ tissue-resident memory T cells. Together, these findings define DC3s as a lineage of inflammatory DCs endowed with a strong potential to regulate tumor immunity.
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•DC3s are phenotypic and functional intermediates between cDC2s and monocytes•GM-CSF alone, but not FLT3L, supports efficient differentiation of DC3s•DC3s do not differentiate via cDC (CDP)- or monocyte-restricted (cMoP) progenitors•DC3s prime TRM cells in vitro and correlate with TRM expansion in primary breast cancer
Bourdely et al. identify human CD88−CD1c+CD163+ DC3s as a pro-inflammatory phagocyte lineage sharing features with monocytes and conventional DCs. DC3s efficiently induce differentiation of CD103+CD8+ T cells in vitro, and their infiltration correlates with CD8+CD69+CD103+ TRM accumulation in breast tumors.
Diagnosis and Treatment of Pancreatic Trauma Kaji, Masahito; Otomo, Yasuhiro; Aiboshi, Junichi ...
Nihon Fukubu Kyukyu Igakkai Zasshi (Journal of Abdominal Emergency Medicine),
2011/09/30, Letnik:
31, Številka:
6
Journal Article
Odprti dostop
We reviewed 16 cases with traumatic pancreatic injuries over a 5-year period. The classification system used was the 2008 version of the Japanese Association for the Surgery of Trauma. Under this ...system, grade IIIb is the most severe type, with pancreatic duct injury. Of our 16 cases 7 were Grade IIIb (head 4, body 2, tail 1). Four cases (IIIb head) were treated with PD and PPPD. Three cases required an emergency room laparotomy (ERL), 2 cases required damage control surgery (DCS) and 1 case required a resuscitation thoracotomy/emergency room thoracotomy (ERT) with a thoracic aorta clamp. Death occurred in 1 case (Grade IIIb Ph). In cases of severe shock due to intra-abdominal hemorrhage, hemostasis via an emergency laparotomy is important. The second priority is the intra-operative diagnosis of the main pancreatic duct. Furthermore, it is necessary to perform DCS.
Previous studies found cDC1s to be protective in early stage anti-GBM disease through Tregs, but pathogenic in late stage Adriamycin nephropathy through CD8+ T cells. Flt3 ligand is a growth factor ...essential for cDC1 development and Flt3 inhibitors are currently used for cancer treatment. We conducted this study to clarify the role and mechanisms of effects of cDC1s at different time points in anti-GBM disease. In addition, we aimed to utilize drug repurposing of Flt3 inhibitors to target cDC1s as a treatment of anti-GBM disease. We found that in human anti-GBM disease, the number of cDC1s increased significantly, proportionally more than cDC2s. The number of CD8+ T cells also increased significantly and their number correlated with cDC1 number. In XCR1-DTR mice, late (day 12–21) but not early (day 3–12) depletion of cDC1s attenuated kidney injury in mice with anti-GBM disease. cDC1s separated from kidneys of anti-GBM disease mice were found to have a pro-inflammatory phenotype (i.e. express high level of IL-6, IL-12 and IL-23) in late but not early stage. In the late depletion model, the number of CD8+ T cells was also reduced, but not Tregs. CD8+ T cells separated from kidneys of anti-GBM disease mice expressed high levels of cytotoxic molecules (granzyme B and perforin) and inflammatory cytokines (TNF-α and IFN-γ), and their expression reduced significantly after cDC1 depletion with diphtheria toxin. These findings were reproduced using a Flt3 inhibitor in wild type mice. Therefore, cDC1s are pathogenic in anti-GBM disease through activation of CD8+ T cells. Flt3 inhibition successfully attenuated kidney injury through depletion of cDC1s. Repurposing Flt3 inhibitors has potential as a novel therapeutic strategy for anti-GBM disease.
•cDC1s are pathogenic in anti-GBM disease through activating CD8+ T cells.•Flt3 inhibitor depleted cDC1s selectively, resulting in attenuation of kidney injury.•Flt3 inhibition is a novel therapy for anti-GBM disease, with accelerated translational potential through drug repurposing.
Single-cell RNA sequencing (scRNA-seq) is a powerful tool for defining cellular diversity in tumors, but its application toward dissecting mechanisms underlying immune-modulating therapies is scarce. ...We performed scRNA-seq analyses on immune and stromal populations from colorectal cancer patients, identifying specific macrophage and conventional dendritic cell (cDC) subsets as key mediators of cellular cross-talk in the tumor microenvironment. Defining comparable myeloid populations in mouse tumors enabled characterization of their response to myeloid-targeted immunotherapy. Treatment with anti-CSF1R preferentially depleted macrophages with an inflammatory signature but spared macrophage populations that in mouse and human expresses pro-angiogenic/tumorigenic genes. Treatment with a CD40 agonist antibody preferentially activated a cDC population and increased Bhlhe40+ Th1-like cells and CD8+ memory T cells. Our comprehensive analysis of key myeloid subsets in human and mouse identifies critical cellular interactions regulating tumor immunity and defines mechanisms underlying myeloid-targeted immunotherapies currently undergoing clinical testing.
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•scRNA-seq analyses highlight conserved myeloid subsets in human and murine CRC•Two distinct TAM subsets show inflammatory and angiogenic signatures, respectively•Two distinct TAM subsets show differential sensitivity to CSF1R blockade•Anti-CD40 activates specific cDC1s and expands Th1-like and CD8+ memory T cells
Combined scRNA-seq analyses on the tumor microenvironment in colorectal cancer and murine tumor models identify distinct myeloid populations that convey differential sensitivity to CSF1R blockade and define concerted immune responses involving dendric cells and T cells upon anti-CD40 treatment.
To examine the use of Double Crush Syndrome (DCS) hypothesis in CTS patients in order to support or disguard the theory.
This study was conducted on 80 adult patients, 40 presenting with brachialgia ...(Group I) and 40 patients claiming of failed CT release operation (Group II). Diagnostic work up included neurological examination, MRI of cervical spine, Phalens, Tinel’s sign, EMG examination and motor and sensory nerve conduction studies.
EMG examination and nerve conduction studies results show 10 cases with CTS (25%), 20 cases (50%) with DCS and 10 cases (25%) with cervical radiculopathy in group I, while group II proved 10 cases (25%) with CTS and 30 cases (75%) with DCS. Accordingly, studied patients showed 20 cases with CTS (25%), 50 cases with DCS (62.5%) and only 10 cases with cervical radiculopathy alone (12.5%). When comparing the first nerve conduction studies of Group II before the operation and the follow up nerve conduction studies of the same group after the operation we found 32 cases (80%) with improvement of the NCS and 8 cases (20%) with deterioration of the nerve conduction studies results.
The double crush syndrome element should be excluded whenever examining for CTS, to guide for treatment.
DCS hypothesis was supported by this sudy.
The double crush concept has gained some popularity among chiropractors because it seems to provide a rationale for evaluating the condition of the cervical roots when treating CTS, which was supported by this study.
•Alhagi honey polysaccharides could increase pIgR secretion in Caco-2 cell in vitro.•Alhagi honey polysaccharides could significantly induce DCs maturation in vitro.•Alhagi honey polysaccharides ...could enhance sIgA in gut of cyclophosphamide-mice.•Alhagi honey polysaccharides could activate the DCs in cyclophosphamide-mice.
It remains a huge challenge to recover the intestine immune function for the treatment of intestinal mucosal damage from chemotherapy with cyclophosphamide (CY). Alhagi honey polysaccharide (AH) has immunomodulation pharmacological activity, but the effect and mechanism on the intestinal immune system of CY-mice remain unclear.
In this experiment, the immunomodulatory activity of AH on intestinal immune in CY-mice and its mechanism of regulating the intestinal immune system was investigated.
The experiment studied the immunomodulatory activity of AH on the intestinal immune system and its mechanism for the first time from in vitro and in vivo experiments. We investigated the immunomodulatory effects of AH on Caco-2 and dendritic cells (DCs) in vitro by using western blot (WB), flow cytometry, quantitative real-time PCR (qPCR), and ELISA methods. In vivo experiment, the immunosuppressive mouse model was established through being given intraperitoneal injection with CY (80 mg/kg) for 3 days. Then, mice oral administration of 800 mg/kg AH and 40 mg/kg levamisole hydrochloride for a week. Immunofluorescence, flow cytometry, ELISA, qPCR and WB were applied to examine the immunomodulatory activity of AH on the intestinal immune function of CY-mice, as well as the function of AH on the concentration of SCFAs in cecum by Gas chromatographic analysis.
In vitro experiments, AH could significantly stimulate the expression of pIgR protein in Caco-2. It could also induce the DCs maturation and release the cytokines to regulate the immune response. In vivo experiments, AH could remarkably stimulate the DCs maturation and secrete more CCL20 to recruit DCs, then induce the T (CD4+ and CD8+) and B cells proliferation and activation. Moreover, it could further induce T helper cells to differentiate and secrete cytokines to enhance the secretion of sIgA. Furthermore, it also directly activated DCs and released cytokines to increase the content of pIgR, J-chain, and IgA+ cells in intestine, thereby enhancing the secretion of sIgA to protect the intestine. In addition, AH could obviously strengthen the SCFAs production in cecum to regulate the intestinal immune dysfunction induced by CY.
In summary, oral administrated AH exhibits great benefits for treating CY-induced intestinal immunosuppression, and the mechanism of action mainly involves sIgA, DCs, SCFAs.
•TD-DCS brain detection is severely affected by present optoelectronic devices.•CW-DCS is currently still superior to TD-DCS in brain functional detection at 830 nm.•With advance of optoelectronics, ...TD-DCS detection ability can be enhanced.
Diffuse correlation spectroscopy (DCS) is an optical technique originally used for measuring dynamic properties of multiple scattering media. Depending on the type of light source used in the system, DCS can be classified as continuous wave DCS (CW-DCS) or time-domain DCS (TD-DCS). With pathlength-resolved measurement, TD-DCS can theoretically achieve a higher sensitivity detection than CW-DCS on dynamics in deep tissue. However, TD-DCS is affected by more factors than CW-DCS such as the instrument response function (IRF), finite coherence length of the light source (Lc), photon detection efficiency (Q), thus the detection ability in the application of measuring cerebral blood flow (CBF) may be degraded. To elucidate this, we used a simulation approach with a realistic head model to show the detection ability of the two DCS techniques on measuring the functional change in CBF with the same incident light wavelength (830 nm), incident light power (75 mW) and single mode detection fiber. The result reveals that TD-DCS is less sensitive than CW-DCS in detecting human brain function in the condition of available optoelectronic devices at 830 nm. This simulation work may also provide a solution to improve the detection ability of TD-DCS on human brain.
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