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Background Primary intussusception in children is a common acute abdominal disease. The cause of this disease is still not fully understood. Many articles have reported that children with intussusception are often accompanied by hyperplasia of mesenteric lymph nodes and submucosal lymphoid tissue of the terminal ileum. Therefore, hyperplasia of intestinal-associated lymphoid tissue (mesenteric lymph nodes and submucosal lymphoid tissue of the intestinal tract) may be one of the main causes of intussusception. However, the characteristics and differences of intestinal-associated lymphoid tissues in healthy children and children with intussusception at different ages have not been reported. In addition, the relationship between mesenteric lymph nodes and intestinal submucosal lymphatic tissue also needs to be further understood. Methods 73 patients with intussusception during the recovery phase who were treated in our hospital from October 2019 to October 2021 were collected as the observation group, while 101 children with healthy physical examination or diseases unrelated to intestinal lymphoid hyperplasia were collected as the control group. They were divided into different age groups of 1–6 months, 7–12 months, 13–18 months, 19–24 months, 25–36 months, 3–4 years, 5–6 years, and 7–8 years old. Ultrasonography was used to explore and scan mesenteric lymph nodes in fixed areas of the right lower abdomen and around the umbilicus. The size (cm 3 ) and number (n) of detectable lymph nodes in each region were recorded and calculated, and the total mesenteric lymph node volume (cm 3 ) of the right lower abdomen (RLTMLNV) and periumbilical region (PTMLNV) was calculated, respectively. The total mesenteric lymph node volume of each region in different ages of the two groups was analyzed. Results (1) There were significant differences between the control group and the observation group in the right lower abdominal total mesenteric lymph nodes volume (RLTMLNV) and the periumbilical total mesenteric lymph nodes volume (PTMLNV) (P = 0.001). The mesenteric lymph nodes in the observation group showed severe hyperplasia. (2) Children with intussusceptions are usually accompanied by severe mesenteric lymphoid hyperplasia. The mean volume value of RLTMLNV was greater than that of PTMLNV. Especially within 2 years of age, the mean value of RLTMLNV was significantly higher than that of PTMLNV with statistical significance (P < 0.05). (3) In normal children (control group), lymph nodes in the right lower abdomen and periumbilical area showed low hyperplasia, and there was a significant difference between age groups of < 2 years old and 2–8 years old (p = 0.001). In the children with intussusception (observation group), the hyperplasia of mesenteric lymph nodes in the right lower abdomen and around the umbilicus was severe. There was no significant difference in the proliferation of mesenteric lymphoid tissue among different age groups in the right lower abdomen (P = 0.834). There was also no significant difference in hyperplasia of periumbilical mesenteric lymphoid tissue among different age groups (P = 0.097). Conclusions Our research shows: (1) The occurrence of primary intussusception in children is related to the hyperplasia of intestinal-associated lymphoid tissue. (2) Children with intussusceptions were usually accompanied by severe mesenteric lymphoid hyperplasia. The mesenteric lymphoid hyperplasia was more evident in the right lower abdominal ileocecal area than in the periumbilical area before 2 years of age. RLTMLNV has better predictability of intussusception than PTMLNV. The occurrence of intussusceptions was more closely related to the hyperplasia of intestinal-associated lymphoid tissue in the right lower abdomen. (3) Normal children showed a low degree of mesenteric lymphoid hyperplasia before 2 years old, moderate hyperplasia after 2 years old, and mesenteric lymphoid hyperplasia in the right lower abdominal ileocecal area was basically the same as the periumbilical area. The lymphatic tissue of the right lower abdomen and periumbilical mesentery in children with intussusceptions showed severe hyperplasia, and there were no significant differences among different age groups.

Susceptibility to pathogen infections and efficacy of vaccination highly depend on the immune status of the piglet. Here, we measured immunocytes in piglets from birth to weaning to elucidate how immunocyte populations change during development and are affected by weaning. Crossbred piglets were used. Suckling piglets were euthanized at 1, 7, 14, 21, 28 or 35 days old (3~4 piglets at each time point). In addition, seven piglets were weaned at 21 days old, with four being euthanized at 28 days old and the remaining at 35 days old. Piglet carcasses were dissected, and blood, mesenteric lymph nodes (MLN) and spleen were sampled. In total, seven antibodies were used to stain the immunocyte population. Dynamics of myeloid (CD3–SWC3+CD16+), natural killer (NK; CD3–SWC3–CD16+), killer T (CD3+CD8+), helper T (CD3+CD4+) and B (CD3–CD21+) cells were analyzed. Percentage of innate immunity cells such as myeloid cells declined (p < 0.05) from the first day after birth. In contrast, percentage of NK cells increased in piglets while they were still suckling. Killer T, helper T, and B cell populations increased around 2~3 weeks after birth. No significant differences in the populations of the evaluated cell types were observed between suckling and weaned piglets at least for 14 days post weaning.

The aim of this study was to clarify the clinical impact of inferior mesenteric lymph node (IMLN) metastasis from cancer of the sigmoid colon or rectum. A total of 952 patients underwent curative surgery with IMLN dissection for either sigmoid colon cancer or rectal cancer from January 2000 to August 2018. Of these, 26 (2.7%) were pathologically diagnosed with IMLN metastasis. Excluding 1 patient, 25 patients were retrospectively investigated for clinicopathological characteristics and long-term outcomes. Specifically, the clinical course of patients with recurrence was meticulously scrutinised. Of the 25 patients, 14 (56%) had recurrence during the follow-up period. The 5-year recurrence-free survival was 31.2%, and 5-year overall survival was 59.7%. No serious morbidity, such as anastomotic leakage, was observed. Of the 14 patients with recurrence, 6 underwent secondary surgery with curative intent and 5 of the 6 patients remained cancer-free. In contrast, 8 patients were treated with chemotherapy, radiotherapy or best supportive care. Although IMLN metastasis was strongly associated with recurrence, long-term survival could be expected in most cases. Furthermore, there could be a chance for complete cure in patients with recurrence if secondary surgery is successfully carried out.

Mesenteric lymph nodes (mLNs) are sentinel sites of enteral immunosurveillance and immune homeostasis. Immune cells from the gastrointestinal tract (GIT) are constantly recruited to the mLNs in steady-state and under inflammatory conditions resulting in the induction of tolerance and immune cells activation, respectively. Surgical dissection and transplantation of lymph nodes (LN) is a technique that has supported seminal work to study LN function and is useful to investigate resident stromal and endothelial cell biology and their cellular interactions in experimental disease models. Here, we provide a detailed protocol of syngeneic mLN transplantation and report assays to analyze effective mLN engraftment in congenic recipients. Transplanted mLNs allow to study T cell activation and proliferation in preclinical mouse models. Donor mLNs proved viable and functional after surgical transplantation and regenerated blood and lymphatic vessels. Immune cells from the host completely colonized the transplanted mLNs within 7-8 weeks after the surgical intervention. After allogeneic hematopoietic cell transplantation (allo-HCT), adoptively transferred allogeneic CD4 + T cells from FVB/N (H-2 q ) mice homed to the transplanted mLNs in C57BL/6 (H-2 b ) recipients during the initiation phase of acute graft-versus-host disease (aGvHD). These CD4 + T cells retained full proliferative capacity and upregulated effector and gut homing molecules comparable to those in mLNs from unmanipulated wild-type recipients. Wild type mLNs transplanted into MHCII deficient syngeneic hosts sufficed to activate alloreactive T cells upon allogeneic hematopoietic cell transplantation, even in the absence of MHCII + CD11c + myeloid cells. These data support that orthotopically transplanted mLNs maintain physiological functions after transplantation. The technique of LN transplantation can be applied to study migratory and resident cell compartment interactions in mLNs as well as immune reactions from and to the gut under inflammatory and non-inflammatory conditions.

Food allergy now affects 6%–8% of children in the Western world; despite this, we understand little about why certain people become sensitized to food allergens. The dominant form of food allergy is mediated by food-specific immunoglobulin E (IgE) antibodies, which can cause a variety of symptoms, including life-threatening anaphylaxis. A central step in this immune response to food antigens that differentiates tolerance from allergy is the initial priming of T cells by antigen-presenting cells (APCs), primarily different types of dendritic cells (DCs). DCs, along with monocyte and macrophage populations, dictate oral tolerance versus allergy by shaping the T cell and subsequent B cell antibody response. A growing body of literature has shed light on the conditions under which antigen presentation occurs and how different types of T cell responses are induced by different APCs. We will review APC subsets in the gut and discuss mechanisms of APC-induced oral tolerance versus allergy to food identified using mouse models and patient samples.

Background Small intestinal neuroendocrine tumors (SI-NETs) are uncommon, with an annual incidence of about 1 per 100,000 individuals. The primary tumor (PT) is generally small, but nevertheless the majority of patients have mesenteric lymph node metastases and liver metastases at diagnosis. Our aim was to identify prognostic factors for survival and to evaluate outcome after surgery in SI-NET patients. Material and Methods We included 603 consecutive patients (325 men; age at diagnosis 63 ± 11 years [mean ± SD]) with histopathologically verified SI-NET, who were diagnosed between 1985 and 2010. Hospital charts were reviewed and were scrutinized for carcinoid heart disease (CHD), flush and/or diarrhea, proliferation by Ki-67 index, mesenteric lymph node metastases (m.lgllm), distant abdominal lymph node metastases (da.lgllm), liver tumor load (LTL), extra-abdominal metastases (EAM), locoregional resective surgery, as well as debulking of LTL, and adverse events after surgery. Results Median overall survival (OS) was 8.4 years; 5-year OS was 67%, and 5-year relative survival was 74%. Independent prognostic factors by univariate and multivariate analysis were age at diagnosis, CHD, m.lgllm, da.lgllm, LTL, EAM, peritoneal carcinomatosis (PC), and proliferation. Locoregional resective surgery was associated with increased survival on crude and multivariate analysis. The 30-day mortality in our institution after initial locoregional resective surgery was 0.5% (1/205). Conclusions For the first time, m.lgllm and da.lgllm, LTL, PC, and EAM are demonstrated to be independent prognostic factors by multivariate analysis. Locoregional removal of the PT/m.lgllm. was a positive prognostic factor by crude and adjusted analysis and may influence survival.

Dendritic and monocytic cells co-operate to initiate and shape adaptive immune responses in secondary lymphoid tissue. The complexity of this system is poorly understood, also because of the high phenotypic and functional plasticity of monocytic cells. We have sequenced mononuclear phagocytes in mesenteric lymph nodes (LN) of three adult cows at the single-cell level, revealing ten dendritic-cell (DC) clusters and seven monocyte/macrophage clusters with clearly distinct transcriptomic profiles. Among DC, we defined LN-resident subsets and their progenitors, as well as subsets of highly activated migratory DC differing in transcript levels for T-cell attracting chemokines. Our analyses also revealed a potential differentiation path for cDC2, resulting in a cluster of inflammatory cDC2 with close transcriptional similarity to putative DC3 and monocyte-derived DC. Monocytes and macrophages displayed sub-clustering mainly driven by pro- or anti-inflammatory expression signatures, including a small cluster of cycling, presumably self-renewing, macrophages. With this transcriptomic snapshot of LN-derived mononuclear phagocytes, we reveal functional properties and differentiation trajectories in a “command center of immunity”, and identify elements that are conserved across species.

Background Neuroendocrine tumors of the small intestine commonly metastasize to regional lymph nodes (LNs). Single-institution reports suggest that removal of LNs improves outcome, but comprehensive data are lacking. We hypothesized that the extent of lymphadenectomy reported in a large administrative database would be associated with overall survival for jejunal and ileal neuroendocrine tumors. Methods A search of the Surveillance Epidemiology and End Results database was performed for patients with jejunal and ileal neuroendocrine tumors from 1977 to 2004. Descriptive patient characteristics were collected to include age at diagnosis, sex, race, grade, primary tumor size, LN status, number of LNs resected, presence of distant metastasis, and the type of operation. Statistical analyses were limited to patients with only one primary tumor to exclude patients with other malignancies. Univariate and multivariate analyses were performed to analyze the number of LNs resected and the LN ratio (number of positive LNs/total number of LNs removed) to determine the effect on cancer-specific survival. Results Altogether, 1,364 patients were included in this analysis. Removal of any LNs was associated with improved cancer-specific survival when compared to patients with no LN removal reported ( p  = 0.0027) on univariate analysis. Among those who had any LNs removed, a median of eight LNs were identified in resection specimens with a median LN ratio of 0.29 (range 0–1). On multivariate analysis (adjusting for age and tumor size), patients with >7 LNs removed experienced better cancer-specific survival than those with ≤7 LNs removed (median survival not reached vs. 140 months): hazard ratio and 95 % confidence interval were 0.573 (0.402, 0.817) ( p  = 0.002). Conclusions This review of a large number of surgical patients demonstrates that regional mesenteric lymphadenectomy in conjunction with resection of the primary tumor is associated with improved survival of patients with small bowel neuroendocrine tumors.

Ciprofloxacin (Cipro) has been associated with various adverse effects, including potential toxicity to the immune system. This study investigates the immunotoxic effects of Cipro and examines the possible protective role of vitamin C (VitC) using rats. Although rats can synthesize VitC, they serve as a relevant model for evaluating drug effects and immune responses due to their physiological and immunological similarities to humans. A total of 40 rats were divided into four groups ( n  = 10). The Cipro group received 750 mg/kg of Cipro orally each day for five days. The VitC-Cipro group was administered 200 mg/kg of VitC orally one hour prior to receiving Cipro daily for five days. The VitC group received the same dose of VitC, while the Control group was given 0.9% normal saline daily for five days. Levels of interleukin-4 (IL-4), interleukin-10 (IL-10), and interferon-gamma (INF-γ) were measured in serum. Histopathological examinations of mesenteric lymph nodes were also conducted. The Cipro group exhibited significantly lower levels of IL-4 compared to all other groups ( P  < 0.05). Similarly, INF-γ levels were significantly reduced in the Cipro group compared to the VitC-Cipro group ( P  < 0.05) and the Control group ( P  < 0.01). No significant differences in IL-10 levels were observed among the groups ( P  > 0.05). Histological analysis revealed degenerative changes in the lymph nodes of the Cipro group, characterized by a moth-eaten appearance, tingible body macrophages, localized hemorrhage, and reactive eosinophilia. Tissue sections from the VitC-Cipro group showed a reduced number of lymphocytes with uneven distribution in the paracortex reticular tissue. These alterations in interleukin levels and lymph node histology may indicate ciprofloxacin-induced immunotoxicity. Furthermore, the ameliorative effects of VitC against Cipro toxicity suggest its potential utility in cases of antibiotic overdose.

Abstract Background and Aims Innate immune cells, including dendritic cells (DCs), monocytes (Mono), macrophages (Mac), natural killer (NK), and innate lymphoid cells (ILC), contribute to chronic inflammation in lymphoid tissues. Here, we characterized the innate immune cell landscape in inflamed mesenteric lymph nodes (MLNs) of patients with inflammatory bowel diseases (IBD) at the single-cell level. Methods Surgically resected colonic MLNs were obtained from patients with Crohn’s disease (CD; n = 3), ulcerative colitis (UC; n = 3), non-inflamed UC (n = 1), and non-IBD (n = 2). CD45+CD3−CD19− non-T/non-B cells were FACS-sorted to capture rare innate immune cells. Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) was performed on the BD Rhapsody platform alongside multiparameter flow cytometry staining. Results CITE-seq analysis unveiled the molecular signature of 11 Mono/Mac/DC (MMDC) and 7 NK/ILC enriched clusters in human MLNs. DC clusters included 3 newly characterized DC clusters such as CD1c/CD163/VCAN/CD64-expressing DC3; AXL-expressing DCs; and a CD103+ DC subset, expressing LTB, S100B, and IL22RA2 (encoding IL22BP). Mono/Mac clusters comprised inflammatory monocytes, which accumulated in IBD compared to non-IBD MLNs. Among NK/ILC clusters, we identified a cytotoxic ILC subset (IL7R, KLRD1, GNLY), previously not reported in MLNs, reminiscent of cytotoxic ILC1-like cells found in inflamed gut mucosa. Conclusion CITE-seq and flow-cytometry analyses of colonic MLNs from patients with active IBD reveal the molecular signature and cell distribution of previously uncharacterized DC and ILC subpopulations in human MLNs. These findings expand our understanding of immune responses during chronic inflammation in IBD. Lay Summary Using a multifaceted approach, we characterized the molecular signature of dendritic cell (DC) subsets not previously reported in human mesenteric lymph nodes, which include DC3, AS-DCs, and IL22RA/LTB-expressing DCs, and discovered a cytotoxic ILC1-like cell subset within natural killer/innate lymphoid cells clusters. Graphical Abstract Graphical Abstract