Tai Chi Chuan Increases Circulating Myeloid Dendritic Cells

Dendritic cells, the most potent antigen-presenting cells linking innate and adoptive immunity, are thought to be important targets of immune modulators such as exercise. We examined the effect of Tai Chi Chuan (TCC) on dendritic cells. TCC practitioners were further divided to high-level practitioners (TCC-H) and low-level practitioners (TCC-L). The quantities of myeloid and plasmacytoid dendritic cells were estimated by flow cytometry. We examined parameters including age, body weight, body length, body fat, and serum albumin level, in the controls, TCC-H and TCC-L, which did not differ significantly. The mean peak (volume of O₂ utilization) of the TCC-H group was greater than that of the sedentary control group. White blood cell (WBC) count in the entire TCC group was greater than that of the controls. The quantity of myeloid dendritic cells was significantly greater in the TCC group, whereas the quantity of plasmacytoid dendritic cells was similar for both groups. Among the TCC subgroups, the quantity of myeloid dendritic cells, but not plasmacytoid dendritic cells, in the TCC-H group was greater than that of TCC-L practitioners. TCC could increase the number of circulating myeloid dendritic cells, but not plasmacytoid dendritic cells, in a performance level-dependent manner.     

Major Hepatectomy Induces Phenotypic Changes in Circulating Dendritic Cells and Monocytes

Introduction  Patients undergoing major hepatectomy are at increased risk for post-operative morbidity and mortality, and changes in the phenotype of effector cells may predispose these patients to infectious sequelae. Methods  To better understand post-hepatectomy immune responses, peripheral blood from 15 hepatectomy patients was drawn immediately before and after liver resection and on post-operative days 1, 3, and 5. Circulating monocytes and dendritic cells were analyzed by flow cytometry for quantity, phenotype, activation status, human leukocyte antigen DR (HLA-DR) expression, and toll-like receptor-2 and -4 expression. Results  Major hepatectomy increased the numbers of activated CD16^bright blood monocytes and the percentage of activated dendritic cells, although monocyte HLA-DR expression was reduced. These results may represent both dysfunctional antigen presentation and pending anergy, as well as cellular priming of immune effector cells. Better understanding of the alterations in innate immunity induced by hepatectomy may identify strategies to reduce infectious outcomes.     

Involvement of Innate Lymphoid Cells and Dendritic Cells in a Mouse Model of Chemical-induced Asthma

PurposeExposure to low concentrations of toluene diisocyanate (TDI) leads to immune-mediated chemical-induced asthma. The role of the adaptive immune system has already been thoroughly investigated; nevertheless, the involvement of innate immune cells in the pathophysiology of chemical-induced asthma is still unresolved. The aim of the study is to investigate the role of innate lymphoid cells (ILCs) and dendritic cells (DCs) in a mouse model for chemical-induced asthma.MethodsOn days 1 and 8, BALB/c mice were dermally treated (20 µL/ear) with 0.5% TDI or the vehicle acetone olive oil (AOO; 2:3). On days 15, 17, 19, 22 and 24, the mice received an oropharyngeal challenge with 0.01% TDI or AOO (1:4). One day after the last challenge, airway hyperreactivity (AHR) to methacholine was assessed, followed by an evaluation of pulmonary inflammation and immune-related parameters, including the cytokine pattern in bronchoalveolar lavage fluid, lymphocyte subpopulations of the lymph nodes and their ex vivo cytokine production profile, blood immunoglobulins and DC and ILC subpopulations in the lungs.ResultsBoth DC and ILC2 were recruited to the lungs after multiple airway exposures to TDI, regardless of the prior dermal sensitization. However, prior dermal sensitization with TDI alone results in AHR and predominant eosinophilic airway inflammation, accompanied by a typical type 2 helper T (Th2) cytokine profile.ConclusionsTDI-induced asthma is mediated by a predominant type 2 immune response, with the involvement of adaptive Th2 cells. However, from our study we suggest that the innate ILC2 cells are important additional players in the development of TDI-induced asthma.     

Flagellin Modulates the Function of Invariant NKT Cells From Patients With Asthma via Dendritic Cells

PurposeInvariant natural killer T (iNKT) cells play a critical role in the pathogenesis of asthma. We previously reported the association between circulating Th2-like iNKT cells and lung function in asthma patients and the suppressive effect of Toll-like receptor 5 ligand flagellin B (FlaB) on asthmatic in a mouse model. Thus, we investigated whether FlaB modulates the function of circulating iNKT cells in asthmatic patients.MethodsPeripheral blood mononuclear cells (PBMCs) were treated with FlaB, and the secreted and intracellular cytokines of iNKT cells were evaluated by using ELISA and flow cytometry, respectively, following stimulation with α-galactosylceramide. Foxp3⁺ iNKT cells were also measured. To determine the effect of FlaB-treated dendritic cells (DCs) on iNKT cells, we co-cultured CD14⁺ monocyte-derived DCs and T cells from patients with house dust mite-sensitive asthma and analyzed intracellular cytokines in iNKT cells.ResultsA reduction of IL-4 and IL-17 production by iNKT cells in PBMCs after FlaB treatment was alleviated following blocking of IL-10 signaling. A decrease in the frequencies of IL-4⁺ and IL-17⁺ iNKT cells by FlaB-treated DCs was reversed after blocking of IL-10 signaling. Simultaneously, an increase in Foxp3⁺ iNKT cells induced by FlaB treatment disappeared after blocking of IL-10.ConclusionsFlaB may inhibit Th2- and Th17-like iNKT cells and induce Foxp3⁺ iNKT cells by DCs via an IL-10-dependent mechanism in asthmatic patients. In patients with a specific asthma phenotype associated with iNKT cells, FlaB may be an effective immunomodulator for iNKT cell-targeted immunotherapy.     

Langerhans Cells and Extra-Epidermal Dendritic Cells

S-100 protein was demonstrated in the cytoplasm of dendritic cells (DCs) in normal and pathologic lymphoid tissues and epidermis in man and several other species. The presence of S-100 protein served to distinguish these cells from other mononuclear cells, most importantly from those of macrophage/histiocyte lineage. Fractionation procedures to isolate and enrich suspensions of DCs were coupled with immunocytochemical techniques to identify S-100-positive cells. Langerhans cells in the epidermis and in aural cholesteatomata and nodal, splenic, and thymic interdigitating cells were S-100-positive. Lymph node and splenic follicular dendritic cells (except in rats) were negative, indicating that this DC may be a separate cell type.     

Exposure to Bacillus anthracis Capsule Results in Suppression of Human Monocyte-Derived Dendritic Cells

The antiphagocytic capsule of Bacillus anthracis is a major virulence factor. We hypothesized that it may also mediate virulence through inhibition of the host''s immune responses. During an infection, the capsule exists attached to the bacterial surface but also free in the host tissues. We sought to examine the impact of free capsule by assessing its effects on human monocytes and immature dendritic cells (iDCs). Human monocytes were differentiated into iDCs by interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) over 7 days in the presence of capsule derived from wild-type encapsulated B. anthracis Ames (WT) or a control preparation from an isogenic B. anthracis Ames strain that produces only 2% of the capsule of the WT (capA mutant). WT capsule consistently induced release of IL-8 and IL-6 while the capA mutant control preparation elicited either no response or only a minimal release of IL-8. iDCs that were differentiated in the presence of WT capsule had increased side scatter (SSC), a measure of cellular complexity, when assessed by flow cytometry. iDCs differentiated in the presence of WT capsule also matured less well in response to subsequent B. anthracis peptidoglycan (Ba PGN) exposure, with reduced upregulation of the chemokine receptor CCR7, reduced CCR7-dependent chemotaxis, and reduced release of certain cytokines. Exposure of naive differentiated control iDCs to WT capsule did not alter cell surface marker expression but did elicit IL-8. These results indicate that free capsule may contribute to the pathogenesis of anthrax by suppressing the responses of immune cells and interfering with the maturation of iDCs.     

树突状细胞与自身免疫的关系

树突状细胞（DC）是一类专职抗原递呈细胞（APC）,通过传导不同的调节信号调节T细胞应答或耐受。因此,DC很有可能成为免疫治疗的有力工具和靶点。近来很多数据表明DC在启动自身免疫应答中发挥重要作用。通过分析啮齿类动物和人体自身免疫病中的DC表型和DC—T细胞的相互作用可以阐明自身免疫病的部分发病机制,并且可以通过调节异常DC的功能达到免疫治疗的目的。     

The Role of Plasmacytoid and Myeloid Dendritic Cells in Induction of Asthma in a Mouse Model and the Effect of a TLR9 Agonist on Dendritic Cells

Purpose

To determine the role of plasmacytoid dendritic cells (pDC) and myeloid dendritic cells (mDC) in priming effector T cells to induce allergy, and to evaluate the effect of immunostimulatory sequences (ISS, TLR9 agonist) on dendritic cells.

Methods

Cultured mDC and pDC with/without ISS were injected intratracheally into sensitized Balb/C mice. Mice were sacrificed, and then pulmonary function tests, bronchoalveolar lavage (BAL), cell counts, and cytokine levels were evaluated. Migration of dendritic cells was also evaluated after ISS administration.

Results

In mice injected with mDC, airway hyperresponsiveness, eosinophil counts, and Th2 cytokine levels in BAL increased with increasing numbers of mDC injected. However, in mice injected with pDC, none of these changed, suggesting poor priming of T cells by pDC. In addition, mDC pulsed with ISS inhibited asthmatic reactions, and ISS administration inhibited migration of DC to the lung.

Conclusions

We suggest that pDC played a limited role in priming T cells in this asthma model and that mDC played a major role in inducing asthma. In addition, ISS inhibited migration of DC to the lung.     

Intrathyroidal Dendritic Cells, Epitheloid Cells, and Giant Cells in Iodine Deficient Goiter

Immunohistochemistry and immunofluorescence were performed on thyroid sections of 44 consecutive patients undergoing thyroid surgery for goiter due to iodine deficiency. Sections were compared with specimens from ten individuals without goiters from the same endemic area, with specimens from ten sporadic nontoxic goiter patients, and with specimens from an area with sufficient iodine supply from nine healthy subjects. Cells were characterized using monoclonal antibodies to the CR3 receptor (CD11b) and the p150/95 antigen (CD11c) present on macrophages, to HLA-DR, to antigen presenting cells (RFD1), to T helper (CD4) and to T suppressor/cytotoxic cells (CD8), and with a polyclonal antibody to human cytokeratin. In iodine deficient goiters, focal aggregates were found of RFD1-positive dendritic cells. Furthermore, RFD1-positive epitheloid cells were seen. In 27% of cases, these epitheloid cells completely filled the thyroid follicles. Within the epitheloid cell clusters, multinucleated giant cells could be detected that carried the macrophage markers. Dendritic cells, epitheloid cells, and giant cells were strongly HLA-DR positive. In nongoitrous thyroids from the endemic area such aggregates could also be seen but they were more sparse and were RFD1 negative. Giant cells were absent there. In normal thyroids with sufficient iodine supply, only a few isolated dendritic cells were seen. All except RFD1, which was negative, showed the same marker pattern. In sporadic nontoxic goiters from an area with sufficient iodine supply, dendritic cells occurred in much higher numbers than in the normal thyroids from that area, and they were RFD1 positive. They never aggregated as in iodine deficiency, and giant cells were not observed. These observations on iodine deficient goiter strongly suggest involvement of active antigen-presenting cells in this disorder. However, the immunohistologic difference between this disease and sporadic goiter suggests different underlying mechanisms.     

趋化因子与树突状细胞

树突状细胞(DC)是骨髓来源的专职抗原呈递细胞。DC可引起T细胞活化和耐受从而启动和抑制免疫反应。DC居留在所有组织和器官,在活化后可移动到周围淋巴器官,呈递抗原至T区的T细胞。由于DC在T细胞活化中的中心作用,在治疗学上利用DC对免疫系统递送阳性和阴性信号引发广泛兴趣。不同成熟阶段的DC,与趋化因子之间相互作用。该综述主要描述DC与趋化因子的交互作用。     

Dendritic Cells and Contact Dermatitis

Contact dermatitis is a biological response to simple chemicals in the skin. Although it is well known that allergic contact dermatitis is mediated by the immune system, it is still uncertain whether it is a kind of protective response or it is simply an unnecessary response. We have demonstrated the following: (1) haptens activate Langerhans cells in the initiation phase of murine allergic contact dermatitis in vivo, (2) haptens activate human monocyte-derived dendritic cells in vitro, (3) the activation of dendritic cells by haptens is primarily mediated by the activation of p38 mitogen-activated protein kinase (MAPK), and (4) the activation of p38 MAPK is mediated by stimulation related to an imbalance of intracellular redox. Based on these observations, we will discuss the biological significance of contact dermatitis. In addition, we will review some up-to-date findings on Langerhans cell biology. Grants: This study was supported in part by the 21st COE program of Tohoku University and by new Energy and Industrial Technology Development Organization.     

5-Lipoxygenase Pathway, Dendritic Cells, and Adaptive Immunity

5-lipoxygenase (5-LO) pathway is the major source of potentproinflammatory leukotrienes (LTs) issued from the metabolism ofarachidonic acid (AA), and best known for their roles in thepathogenesis of asthma. These lipid mediators are mainly releasedfrom myeloid cells and may act as physiological autocrine andparacrine signalling molecules, and play a central role inregulating the interaction between innate and adaptive immunity. The biological actions of LTs including their immunoregulatoryand proinflammatory effects are mediated through extracellularspecific G-protein-coupled receptors. Despite their role ininflammatory cells, such as neutrophils and macrophages, LTs mayhave important effects on dendritic cells (DC)-mediated adaptiveimmunity. Several lines of evidence show that DC not only areimportant source of LTs, but also become targets of their actionsby producing other lipid mediators and proinflammatory molecules.This review focuses on advances in 5-LO pathway biology, theproduction of LTs from DC and their role on various cells ofimmune system and in adaptive immunity.     

Image-Based Study of Interferongenic Interactions between Plasmacytoid Dendritic Cells and HSV-Infected Monocyte-Derived Dendritic Cells

Plasmacytoid dendritic cells (pDC) are well-known for their ability to produce large quantities of interferon-α (IFN-α) in response to viruses. In addition, pDC produce IFN-α in response to HSV-infected cells. We demonstrate that both tonsil and PBMC contain pDC that respond to stimulation with HSV either in suspension or in tonsil tissue-fragment culture. We hypothesized that other DC subsets acquire virus in the periphery and deliver the interferongenic signals to the pDC in the draining lymphoid tissue. As a model for pDC/myeloid DC interaction, we studied the interaction of pDC derived from blood with HSV-infected and uninfected monocyte derived dendritic cells (MDDC). Infected, but not uninfected, MDDC induced IFN-α in pDC. To further study pDC/infected MDDC interactions, we labeled MDDC with fluorescent cell trackers PKH67 or CFSE prior to infection with HSV and co-cultured with pDC. Cells were then analyzed using conventional and imaging flow cytometry. In addition, we infected MDDC with a GFP-expressing HSV prior to co-culture with pDC. Using traditional flow cytometry, we observed that pDC became fluorescent after co-incubation with uninfected or infected, fluorescently labeled MDDC, indicating that MDDC transferred fluorescent protein and membrane to pDC. By imaging flow cytometry, we observed formation of conjugates between pDC and MDDC as well as transfer and internalization of cellular components from the labeled MDDC by pDC, with preferential uptake from, and association with, infected vs. uninfected MDDC. These studies demonstrate that MDDC infected with HSV are able to stimulate IFN-α and chemokine production by pDC through the transfer of cellular materials from the HSV-infected MDDC to the pDC. Together, these observations indicate that heterogeneous populations of DC interact to generate an effective IFN-α response.     

Circulating Regulatory T Cells in Endometrial Cancer: A Role for Age and Menopausal Status

Regulatory T cells (Treg) are a sub-population of T cells that suppress self-reactivity and are implicated in immune tolerance towards malignant cells. Circulating Treg cells are increased in several cancers. In endometrial cancer Treg cells have been investigated only in tumour tissues and, in contrast to some other tumours, fewer Treg cells were reported in endometrial cancer compared with benign controls. Flow cytometry was used to determine the frequency of circulating Treg cells in women undergoing hysterectomy for either endometrial cancer (n = 24) or non- cancer-related conditions (n = 21). Circulating Treg cells were more abundant in women with cancer compared to those without (4.68% vs. 3.66%, p = 0.05, Mann-Whitney test). This relationship disappeared, however, when only data from post-menopausal women were included in the analysis. Mean Treg cell frequency was 4.65% in postmenopausal women with cancer (n = 23) and 4.73% in postmenopausal controls (n = 5) (p = 0.9). In women without cancer we found that mean Treg cell frequency was higher in postmenopausal women (4.73%, n = 5) in comparison to premenopausal controls (3.33%, n = 16) (p = 0.02). These results suggest that the increased proportion of Treg cells seen in endometrial cancer patients might be, at least in part, attributed to their postmenopausal status or age.     

Obstructive Apneas Induce Early Release of Mesenchymal Stem Cells into Circulating Blood

Study Objectives:

To investigate whether noninvasive application of recurrent airway obstructions induces early release of mesenchymal stem cells into the circulating blood in a rat model of obstructive sleep apnea.

Design:

Prospective controlled animal study.

Setting:

University laboratory.

Patients or Participants:

Twenty male Sprague-Dawley rats (250–300 g).

Interventions:

A specially designed nasal mask was applied to the anesthetized rats. Ten rats were subjected to a pattern of recurrent obstructive apneas (60 per hour, lasting 15 seconds each) for 5 hours. Ten anesthetized rats were used as controls.

Measurements and Results:

Mesenchymal stem cells from the blood and bone marrow samples were isolated and cultured to count the total number of colony-forming unit fibroblasts (CFU-F) of adherent cells after 9 days in culture. The number of CFU-F from circulating blood was significantly (P = 0.02) higher in the rats subjected to recurrent obstructive apneas (5.00 ± 1.16; mean ± SEM) than in controls (1.70 ± 0.72). No significant (P = 0.54) differences were observed in CFU-F from bone marrow.

Conclusions:

Application of a pattern of airway obstructions similar to those experienced by patients with sleep apnea induced an early mobilization of mesenchymal stem cells into circulating blood.

Citation:

Carreras A; Almendros I; Acerbi I; Montserrat JM; Navajas D; Farré R. Obstructive apneas induce early release of mesenchymal stem cells into circulating blood. SLEEP 2009;32(1):117-119.     

Dendritic Cells,Indoleamine 2,3 Dioxygenase and Acquired Immune Privilege

Dendritic cells (DCs) are specialized to stimulate T cell immunity. Paradoxically, some DCs suppress T cell responses and activate regulatory T cells. In this review, we focus on a potent counter-regulatory pathway mediated by plasmacytoid DCs (pDCs) expressing the immunosuppressive enzyme indoleamine 2,3 dioxygenase (IDO). IDO-expressing pDCs inhibit effector T cell responses, activate regulatory T cells, and attenuate pro-inflammatory responses in settings of chronic inflammation that manifest in clinical syndromes, such as infectious, allergic, and autoimmune diseases; cancer; and transplantation. Thus, IDO-expressing pDCs create immune privilege and provide novel opportunities to improve immunotherapy in multiple disease syndromes.     

Thymic Dendritic Cells and B Cells: Isolation and Function

The thymus is the primary organ in which T cells undergo rearrangement of T cell receptor α and β genes, positive selection for affinity to self MHC products, and elimination (negative selection) of reactivity to self antigens. These events require an interaction of the developing T cell with other cell types in the thymus. The latter include epithelial cells, macrophages, dendritic cells, and the recently described thymic B cells the majority of which are CD5⁺. Here we review the identification and isolation of thymic dendritic cells and CD5⁺ B cells. We consider phenotype, ontogeny, and function, including possible contributions to the induction of self tolerance. Thymic dendritic cells are similar to spleen dendritic cells, but are larger and exhibit a few differences in phenotype. Dendritic cells from both organs are equally potent accessory cells for the MLR and lectin-induced, T cell proliferation. Thymic dendritic cells have higher levels of Fc receptors and support anti-CD3 dependent mitogenesis. Thymic CD5⁺ B cells share phenotypic features with peritoneal CD5⁺ B cells. However thymic B cells neither proliferate nor form antibody producing cells in response to the stimulation with LPS or anti-IgM plus IL-4, but do respond to stimulation with MHC class II-restricted helper T cells. Thymic dendritic cells and CD5⁺ B cells both appear at a similar time in ontogeny, about 14 d of gestation, which is the time T cell differentiation begins to take place. Dendritic cells from spleen, which are potent activators for peripheral T cells, are also potent inactivators for thymic-derived cytotoxic T cells. A correlation between reactivity to MIs products and the expression of TCR-Vβ genes is well documented, and B cells are the primary APC for this antigen. Therefore, thymic CD5⁺ B cells may be a good tool for the investigation of tolerance to Mls products.