Effects of acute aerobic exercise on arterial stiffness in transgender men.

Testosterone replacement therapy (TRT) in transgender men (TM) results in side effects such as elevated triglycerides and increased arterial stiffness. Exercise may be useful to ameliorate such effects, but no studies have examined the effects of acute aerobic exercise in TM. This study aimed to investigate the effects of acute aerobic exercise on arterial stiffness in TM. Thirty-six participants were included, comprising 12 TM (duration of TRT: 57.4 ± 30.3 months), 12 males and 12 females. All participants performed acute aerobic exercise on a treadmill at 50% heart rate reserve for 30 min. Arterial stiffness as measured by brachial-ankle pulse wave velocity (baPWV) was measured before exercise (Pre), 30 min after exercise (Post30), and 60 min after exercise (Post60). Serum sex hormone levels, and serum lipid profile were determined only before exercise. Serum low-density lipoprotein cholesterol (LDL-C) levels before exercise were significantly higher in TM than in males or females (males: p < 0.01; females: p < 0.05). At all points, baPWV in TM was significantly higher than in females (p < 0.05) and significantly lower than in males (p < 0.05). However, when comparing changes in baPWV over time in each group, significant decreases in Post30 and Post60 were seen in males compared to Pre (both p < 0.05), but no significant change after aerobic exercise was seen in TM or females. These results suggest that acute aerobic exercise yield different effects in TM than in males, but is unlikely to reduce arterial stiffness in TM receiving TRT.

Impact of Bifidobacterium adolescentis in patients with abdominal aortic aneurysm: a cross-sectional study.

The relationships between various diseases and the human gut microbiota (GM) have been revealed. However, the relationships between the human abdominal aortic aneurysm (AAA) and GM remains unknown. The aim of this cross-sectional study was to clarify the association between the human AAA and GM. Stool samples from 30 consecutive patients with AAA before aneurysm repair and those of 30 controls without vascular diseases were analyzed by 16S rRNA gene (V3-4) sequencing using an Illumina MiSeq system and QIIME 2. There was no significant difference in age (75 vs. 75 years) or gender (80% vs. 87% males) between the groups. No significant difference in GM composition was observed in principal coordinate analysis between the two groups, whereas the AAA group showed a significantly lower abundance of Bifidobacterium adolescentis (p<0.01) at the species level than the controls. This study demonstrated that the abundance of B. adolescentis decreased in patients with AAA. This is the first study to show the characteristics of the GM in patients with AAA. Studies are needed to reveal if causal relationships exists between the human AAA and GM.

Influence of Menstrual Cycle on Leukocyte Response Following Exercise-Induced Muscle Damage.

We investigated the influence of the menstrual cycle (MC) on leukocyte response after exercise-induced muscle damage (EIMD). During the early follicular (E-FP, n = 12) or mid-luteal phase (M-LP, n = 12), 24 untrained females with eumenorrhea performed 60 eccentric exercises using nondominant arms. Blood samples were collected at pre- and 4, 48, and 96 h postexercise to analyze estradiol and progesterone concentrations, leukocyte count and fractionation, and creatine kinase (CK) activity. We also assessed the maximal voluntary isometric contraction torque of elbow flexion, range of motion in the elbow joint, upper-arm circumference, and muscle soreness as indirect muscle damage markers at pre-; immediately post-; and 4, 48, and 96 h postexercise. The percent change in neutrophil counts from pre- to 4 h postexercise was lower in M-LP than in E-FP (E-FP, 30.7% [15.9-65.7%] vs. M-LP, 10.3% [-2.3-30.0%]; median [interquartile range: 25-75%]; p = 0.068). Progesterone concentration at pre-exercise was significantly negatively correlated with the percent change in neutrophil counts from pre- to 4 h postexercise in M-LP (r = -0.650, p = 0.022). MC did not affect CK activity or other muscle damage markers. Thus, progesterone concentration rather than MC may be related to neutrophil response following EIMD.

Growth of various obligate and facultative anaerobic intestinal bacteria in cell culture medium under aerobic and anaerobic culture conditions.

Eight bacterial strains were used in this study to examine the survival of intestinal bacteria in immune cell cultures under aerobic and anaerobic culture conditions. With the addition of penicillin G and streptomycin, viable Clostridium clostridioforme and Fusobacterium varium cells did not decrease after 6 or 24 hr, even under aerobic conditions. Without antibiotics, eight bacterial strains did not decrease until 4 or 6 hr later, under both aerobic and anaerobic conditions. Escherichia coli numbers increased by more than 10 times under both conditions. In order to examine the effects of live gut bacteria on various immune cells, the viability of bacteria should be checked in cell culture media and under different conditions.

Warm-Up Intensity and Time-Course Effects on Jump Height under Cold Conditions.

With this study, we aimed to investigate the effects of different warm-up intensities on counter-movement jump (CMJ) performance over time under cold conditions. Eleven male collegiate athletes volunteered. The participants performed high-intensity warm-up (HWU) at 80% VO2max and moderate-intensity warm-up (MWU) at 60% VO2max for 15 min on a bicycle ergometer in a laboratory room at 10 °C. CMJ height, vastus lateralis muscle temperature, heart rate, and perceived fatigue were measured before warm-up (Pre), immediately after (Post 0), 10 min after (Post 10), and 20 min after (Post 20). Significant main effects and interactions were found for CMJ height (time, p < 0.001 and ηp2 = 0.859; interaction, p = 0.007 and ηp2 = 0.327). HWU significantly increased CMJ height at Post 0 to Post 20 compared to that at Pre (p < 0.01), whereas MWU increased CMJ height at Post 0 only compared to that at Pre (p < 0.001). The results indicate that HWU achieved an increase in CMJ height for 20 min. MWU changed CMJ height instantly, but the change did not last compared to HWU in a cold environment.

Gastrointestinal disorders and intestinal bacteria: Advances in research and applications in therapy.

Intestinal bacteria coexist with humans and play a role in suppressing the invasion of pathogens, producing short-chain fatty acids, producing vitamins, and controlling the immune system. Studies have been carried out on culturable bacterial species using bacterial culture methods for many years. However, as metagenomic analysis of bacterial genes has been developed since the 1990s, it has recently revealed that many bacteria in the intestine cannot be cultured and that approximately 1,000 species and 40 trillion bacteria are present in the gut microbiota. Furthermore, the composition of the microbiota is different in each disease state compared with the healthy state, and dysbiosis has received much attention as a cause of various diseases. Regarding gastrointestinal diseases, dysbiosis has been reported to be involved in inflammatory bowel disease, irritable bowel syndrome, and non-alcoholic steatohepatitis. Recent findings have also suggested that dysbiosis is involved in colon cancer, liver cancer, pancreatic cancer, esophageal cancer, and so on. This review focuses on the relationship between the gut microbiota and gastrointestinal/hepatobiliary diseases and also discusses new therapies targeting the gut microbiota.

Long-term outcomes of antibiotic combination therapy for ulcerative colitis.

AIMS: An antibiotic combination of amoxicillin, tetracycline and metronidazole (ATM) is effective for ulcerative colitis (UC), but this regimen is discontinued in some cases due to adverse events. This study aimed to assess a revised combination, namely, amoxicillin, fosfomycin and metronidazole (AFM), in UC patients with the goal of reducing side effects while maintaining therapeutic efficacy. METHODS: A prospective open-label trial was undertaken in 104 adult UC patients. A combination of oral amoxicillin (1500 mg), fosfomycin (3000 mg) and metronidazole (750 mg) was administered to patients daily for 2-4 weeks in addition to their conventional medication. Clinical assessment was performed using the Lichtiger index before treatment and at 0, 3, 6, 9 and 12 months and 2 and 3 years. Endoscopic evaluation was performed using the Mayo score before treatment and at 3 and 12 months. RESULTS: The compliance rate was 99.2%. Response and remission rates were 80.8% and 63.5% at completion, 73.1% and 64.4% at 3 months, and 39.4% for both at 12 months, respectively. Of the 41 patients who were in remission at 12 months, 63.4% maintained that status until the 2-year follow-up. Similarly, 69.2% of those in remission at 2 years remained relapse free at the 3-year follow-up. Side effects were observed in 44.2% of the participants. Fever occurred in one patient (1.0%), which was lower than the rate observed with ATM therapy. CONCLUSION: These results indicate that AFM therapy induces remission and is appropriate for long-term maintenance of UC while producing fewer and milder adverse events than ATM therapy. CLINICAL TRIALS: This study was registered in the University Hospital Medical Information Network (No. R000046546).

Gut Microbiota and Chronic Constipation: A Review and Update.

Background: Chronic constipation, including functional constipation and constipation-type irritable bowel syndrome, is a prevalent, multifactorial gastrointestinal disorder, and its etiology and pathophysiology remain poorly understood. Recently studies using 16S rRNA-based microbiota profiling have demonstrated dysbiosis of gut microbiota in chronic constipation. Aims: To provide an overview of recent studies for microbiota in chronic constipation and treatments for chronic constipation using probiotics, prebiotics, synbiotics, antibiotics and fecal microbiota transplantation (FMT). Methods: PubMed searches were performed up to 1 August 2018 using keywords: "IBS," "IBS-C," "irritable bowel syndrome," "irritable bowel syndrome with constipation," "functional constipation," "chronic constipation" in combination with "gut microbiota," "dysbiosis," "gut microflora" for microbiota in chronic constipation, and in combination with "probiotics," "prebiotics," "synbiotics," "antibiotics," and "fecal microbiota transplantation." Results: The findings of gut microbiota in functional constipation are inconsistent, and currently no consensus exists. Although no clear consensus exists, compared with healthy subjects, IBS-C patients have a lower level of Actinobacteria, including Bifidobacteria, in their fecal samples and a higher level of Bacteroidetes in their mucosa. In most randomized controlled and parallel-group trials, probiotics, prebiotics, synbiotics, antibiotics, and FMT therapy for chronic constipation were effective with few side effects. However, there are many studies in a small number and the types of probiotics are different, it is difficult to evaluate the effect. Conclusions: Evidence indicates that dysbiosis of gut microbiota may contribute to functional constipation and constipation-type irritable bowel syndrome. Targeting treatments for the dysbiosis of constipation by probiotics, prebiotics, synbiotics, antibiotics, and FMT may be a new option, especially for refractory constipation to conventional therapies.

Comparative analysis of endoderm formation efficiency between mouse ES cells and iPS cells.

Definitive endoderm (DE) derived from stem cells holds potential to differentiate into hepatocytes. Stem cell therapy using those cells has potential for a treatment of liver disease. To date, various ways of inducing hepatocytes from embryonic stem (ES) cells have been reported by researchers. However, it has not been proved enough that induced pluripotent stem (iPS) cells behave in the same manner as ES cells in endoderm differentiation. The purpose of this study was to establish an efficient method to induce DE from iPS cells, through comparatively analyzing the efficacy of endoderm formation from mouse ES cells. Furthermore, the efficiency of a serum-free medium in the differentiation into DE was investigated. Mouse ES cells and iPS cells were floated in culture medium for 2 or 5 days and embryoid bodies (EB) were formed. Subsequently, DE was induced with 100 ng/ml activin A and 100 ng/ml basic fibroblast growth factor (bFGF). RT-PCR and real-time PCR analyses were carried out at each step to determine the gene expression of EB markers. The difference in cellular proliferation between serum-containing and serum-free media was examined by an MTS assay in EB and DE induction. iPS cells showed the paralleled mRNA expression to ES cells in each step of differentiation into EB, but the levels of expression of Sox17 and Foxa2 were relatively higher in ES cell-derived DE, whereas Cxcr4 expression was higher in iPS cell-derived DE. The utilization of serum-free medium for iPS cells showed significantly favorable cellular proliferation during EB formation and subsequent DE induction. Forming EB for 5 days and subsequently DE induction with activin A and bFGF with serum-free medium was an appropriate protocol in iPS cells. This may represent an important step for generating hepatocytes from iPS cells for the development of cell therapy.

Hepatic differentiation of mouse iPS cells in vitro.

Induced pluripotent stem (iPS) cells are pluripotent and are able to unlimitedly proliferate in vitro. This technical breakthrough in creating iPS cells from somatic cells has noteworthy implications for overcoming the immunological rejection and the ethical issues associated with the derivation of embryonic stem cells from embryos. In the current work, we present an efficient hepatic differentiation of mouse iPS cells in vitro. iPS cells were cultured free floating to induce the formation of embryoid bodies (EB) for 5 days. EB were transferred to a gelatin-coated plate and treated with 100 ng/ml activin A and 100 ng/ml basic fibroblast growth factor (bFGF) for 3 days to induce definitive endoderm. Cells were further cultured for 8 days with 100 ng/ml hepatocyte growth factor (HGF) to generate hepatocytes. Characterization was performed by RT-PCR assay. Functional analysis for albumin secretion and ammonia removal was also carried out. iPS cell-derived hepatocyte-like cells (iPS-Heps) were obtained at the end of the differentiation program. Expression levels of a gestational hepatocyte gene and lineage-specific hepatic genes intensified in iPS-Heps. The production of albumin increased in a time-dependent manner. iPS-Heps were capable of metabolizing ammonia. We present here instant hepatic differentiation of mouse iPS cells using combined 3-day treatments of activin A and bFGF with subsequent 8-day HGF. Our study will be an important step to generate hepatocytes from human iPS cells as a new source for liver-targeted cell therapies.

Isolation and propagation of a human CD133(-) colon tumor-derived cell line with tumorigenic and angiogenic properties.

It has been proposed in human colorectal cancers (CRC) a minority subset of cancer cells within tumors able to initiate tumor growth, defined as cancer stem cells (CSC). Solid human primary colonic and its ovarian metastatic cancer tissues were collected from fresh surgical samples and subsequent xenografts were established in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. The resulting tumors were disaggregated into single-cell suspensions and a CD133(-) cell line (NANK) was newly established and analyzed by flow cytometry. Surface markers of progenitor cells were immunophenotypically analyzed, and expression of stem cell and cancer-related genes was characterized. Secreted angiogenesis-associated molecules were investigated by proteomic array technology. Finally, different numbers of NANK were implanted and their tumor-initiating properties were investigated in NOD/SCID mice. Intraperitoneal injection of NANK in NOD/SCID mice induced tumors with developing progressive peritoneal dissemination and ascites. NANK cells maintained a differentiated phenotype and reproduced the full morphologic and phenotypic heterogeneity of their parental lesions. Noticeably, NANK lacked the expression of conventional CSC markers CD133 and CD44, self-renewal genes Oct-4 and Nanog, but showed the expression of an important gastrointestinal development marker CDX-2 and BMI-1 that is essential in regulating the proliferative activity of normal and leukemic stem cells. In addition, NANK secreted high amounts of important angiogenic cytokines. These results provide a novel and extensive model in human CSC for studying the generation and maintenance of phenotypic heterogeneity in CRC.

Immunohistochemical discrimination of plasmacytoid dendritic cells from myeloid dendritic cells in human pathological tissues.

Until now, no method has been available to discriminate mature plasmacytoid DC (pDC) from myeloid DC (mDC) immunohistochemically. In this study, we report that these DC-subsets can be distinguished in routine pathological sections. Immature and mature monocyte-derived DCs (MoDCs) were S100 calcium binding protein B (S100B)+, while pDCs generated from pDC-precursors were S100B-. In contrast, both mature MoDC and pDC were fascin+. Epidermal Langerhans cells (LCs) were S100B+/fascin-. Although the majority of DCs were S100B+/fascin+ in the dermis with nonspecific inflammation, dermal DCs were mostly S100B-/fascin+ in psoriasis vulgaris, in which type I interferon secreted by pDC-precursors is thought to play a major role. S100B+/fascin+ DCs were accumulated in the superficial lymph node (LN), while they were scarce in the deep LN. In the superficial LN with dermatopathic lymphadenitis, a large number of S100B+/fascin+ DCs were accumulated in the T-zones, where numerous LC-derived DCs are accumulated. In contrast, almost all DCs were S100B-/fascin+ in the superficial LN with Kikuchi's lymphadenitis, in which numerous pDC-precursors are known to be present. In contrast to the superficial LN, the deep LN contained numerous S100B-/fascin+ DCs and a few S100B+ DCs. Thus, the distributions of S100B+ DC or S100B-/fascin+ DC correspond to the putative distribution of mDC or mature pDC, respectively.

Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman's disease.

IgG4-related disease sometimes involves regional and/or systemic lymph nodes, and often clinically and/or histologically mimics multicentric Castleman's disease or malignant lymphoma. In this study, we examined clinical and pathologic findings of nine patients with systemic IgG4-related lymphadenopathy. None of these cases were associated with human herpes virus-8 or human immunodeficiency virus infection, and there was no T-cell receptor or immunoglobulin gene rearrangement. Histologically, systemic IgG4-related lymphadenopathy was classified into two types by the infiltration pattern of IgG4-positive cells: interfollicular plasmacytosis type and intra-germinal center plasmacytosis type. The interfollicular plasmacytosis type showed either Castleman's disease-like features or atypical lymphoplasmacytic and immunoblastic proliferation-like features. By contrast, the intra-germinal center plasmacytosis type showed marked follicular hyperplasia, and infiltration of IgG4-positive cells mainly into the germinal centers, and some cases exhibited features of progressively transformed germinal centers. Interestingly, eight of our nine (89%) cases showed eosinophil infiltration in the affected lymph nodes, and examined patients showed high elevation of serum IgE. Laboratory examinations revealed elevation of serum IgG4 and soluble interleukin-2 receptors. However, the levels of interleukin-6, C-reactive protein, and lactate dehydrogenase were within normal limits or only slightly elevated in almost all patients. One patient showed a high interleukin-6 level whereas C-reactive protein was within the normal limit. Autoantibodies were examined in five patients and detected in four. Compared with the previously reported cases of multicentric Castleman's disease, our patients with systemic IgG4-related lymphadenopathy were significantly older and had significantly lower C-reactive protein and interleukin-6 levels. In conclusion, in our systemic IgG4-related lymphadenopathy showed pathologic features only partially overlapping those of multicentric Castleman's disease, and serum data (especially C-reactive protein and interleukin-6) are useful for differentiating the two. Our findings of eosinophil infiltration in the affected tissue and elevation of serum IgE may suggest an allergic mechanism in the pathogenesis of systemic IgG4-related lymphadenopathy.

Identification and characterization of human thymic cortical dendritic macrophages that may act as professional scavengers of apoptotic thymocytes.

We identify and characterize a special type of macrophage in the human thymic cortex that may act as professional scavengers of apoptotic thymocytes. These are large cells with clear cytoplasm, evenly distributed exclusively in the thymic cortex, and usually contain degraded nuclei in their cytoplasm. They are distinct from ordinary macrophages (OM) in the thymic cortex in expressing fascin, an actin-bundling protein specific for dendritic cells (DC), and in lacking lysozyme (LZM) and CD68. They are also different from DC in lacking major histocompatibility complex (MHC)-class II molecules. To distinguish them from OM and DC, we called them thymic cortical dendritic macrophages (TCDM). Both TCDM and OM are positive for DC-SIGN (CD209) and HAM56, whereas fascin(hi) MHC-class II(hi) medullary DC (mDC) are negative for these antigens. TCDM exhibit either dendritic or plump feature depending on cases examined. Plump TCDM usually contain several degraded nuclei, while dendritic TCDM contain one or two. These degraded nuclei are positive for active caspase-3 (aCasp-3), indicating that they are apoptotic thymocytes. In contrast to TCDM, LZM(hi) CD68(hi) OM are smaller round cells, distributed unevenly throughout the thymus, and do not contain apoptotic thymocytes at all. TCDM tend to adhere to capillaries with their dendrites or they make extensive contacts covering a large portion of the capillaries. Electron microscopic analysis confirmed the extensive contact between TCDM and capillaries and indicated that TCDM possess extremely electron-lucent, abundant cytoplasm with numerous tubulovesicular structures and secondary lysosomes. The finding of numerous condensed nuclei in most of the TCDM indicates that these cells represent a special type of fixed macrophages in the human thymic cortex, and that they play a central role in the clearance of apoptotic thymocytes.

Calorie restriction improves cardiovascular risk factors via reduction of mitochondrial reactive oxygen species in type II diabetic rats.

Uncoupling protein 2 (UCP2) is an important regulator of intracellular reactive oxygen species (ROS) production. We determined the effects of calorie restriction (CR) on the dynamic aspects of mitochondrial ROS production, UCP2, and the nitric oxide (NO)-cGMP pathway in the cardiovascular tissues of type II diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Some rats were on restricted diets (30% reduction from free intake) from age 29 to 42 weeks. Blood glucose, hemoglobin A1c, plasma levels of free fatty acid, triacylglycerol, and plasminogen activator inhibitor-1 in OLETF rats were significantly higher than those in nondiabetic control [Long-Evans Tokushima Otsuka (LETO)] rats at 29 weeks. Mitochondrial ROS production and UCP2 expression significantly increased in the heart and aorta of OLETF rats compared with those in LETO rats. A fibrogenic growth factor, transforming growth factor (TGF)-beta1 in the coronary vessels, endothelial nitric-oxide synthase, and aortic nitrotyrosine were increased in OLETF rats at 42 weeks. In contrast, an index of the NO-cGMP pathway, phosphorylated vasodilator-stimulated phosphoprotein, and superoxide dismutase activity in the aorta were significantly diminished. The relationship between UCP2 and ROS production in the cardiovascular function of diabetic rats being fed a calorie-restricted diet is unknown. These abnormalities in OLETF rats were reversed to normal levels by CR. CR significantly improved the NO-cGMP pathway via normalizing ROS generation in OLETF rats. A decrease in UCP2 expression by CR may be a compensatory mechanism to counteract decreased intracellular oxidative stress. The data suggest that CR may prevent cardiovascular tissues from oxidative stress provoked by diabetes mellitus.

Effect of AOB, a fermented-grain food supplement, on oxidative stress in type 2 diabetic rats.

Reactive oxygen species (ROS) play an important role in the pathogenesis of diabetic complications. Antioxidant Biofactor (AOB) is a mixture of commercially available fermented grain foods and has strong antioxidant activity. This study investigated the effect of AOB supplementation of standard rat food on markers of oxidative stress and inflammation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with type 2 diabetes. Blood glucose, hemoglobin A1c, plasma free fatty acid, triacylglycerol and plasminogen activator inhibitor-1 (PAI-1) were significantly higher in OLETF rats than in non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats at 29 weeks. AOB (6.5% of diet) was given to rats during 29-33 weeks of diabetic phase in OLETF rats. OLETF rats with AOB supplementation showed decreased blood glucose, hemoglobin A1c, triacyglycerol, low density lipoprotein, cholesterol and PAI-1. Mitochondrial ROS production was significantly increased in heart, aorta, liver and renal artery of OLETF rats. Uncoupling protein 2 (UCP2) is known to regulate ROS production. We found aortic UCP2 protein expression increased in OLETF rats, and AOB returned UCP2 expression to normal. Aortic endothelial NO synthase (eNOS) was also increased in OLETF rats more than in LETO rats at 33 weeks. In contrast, phosphorylated vasodilator-stimulated phosphoprotein, an index of the NO-cGMP pathway, was significantly diminished. AOB increased eNOS proteins in LETO and OLETF rats. In conclusion, AOB significantly improved the NO-cGMP pathway via normalizing ROS generation in OLETF rats. The data suggest that dietary supplementation with AOB contributes to nutritional strategies for the prevention and treatment of type 2 diabetes mellitus.

Dendritic cells interacting mainly with B cells in the lymphoepithelial symbiosis of the human palatine tonsil.

The lymphoepithelial symbiosis (LES) of the human palatine tonsil is composed of spindle- or star-shaped epithelial cells forming a loose meshwork, containing numerous lymphocytes and dendritic cells (DCs). In the present study, we immunohistochemically characterized DCs in the LES (LES-DCs). LES-DCs were phenotypically immature DCs that were S100beta+, fascin-, HLA-DR+, CD1a-, CD80-, CD83-, CD86-, and CD123-. The most characteristic feature of LES-DCs was that they contacted many B cells, which were mostly IgM+ IgD+ resting naive B cells. Langerhans cells (LCs) located in the nonsymbiotic squamous epithelium were immature DCs that were S100beta+, fascin-, and CD1a+ and did not contact lymphocytes. In contrast to LES-DCs, interdigitating dendritic cells (IDCs) in the T zone were mature DCs that were HLA-DR+, CD1a-, fascin+, CD80+, CD83+, and CD86+ and contacted numerous CD4+ T cells. Two subsets of IDC, S100beta+ fascin+ IDC (IDC-1) and S100beta- fascin+ IDC (IDC-2), were identified, and the majority of IDCs are IDC-2. In contrast to IDCs, which were distributed in the T-cell area in groups, LES-DCs were distributed along the crypt as if forming a barrier. These findings suggest that LES-DCs are a novel type of DC playing an important role in the induction of humoral immune response against incoming air- or food-borne pathogenic antigens.