1.FLT3 ligand regulates expansion of regulatory T-cells induced by regulatory dendritic cells isolated from gut-associated lymphoid tissues through the Notch pathway.
Na LI ; Jingwei MAO ; Haiying TANG ; Xiaoyan TAN ; Jian BI ; Hao WU ; Xiuli CHEN ; Yingde WANG
Chinese Medical Journal 2025;138(13):1595-1606
BACKGROUND:
Regulatory dendritic cell (DCreg) subset exhibits a unique capacity for inducing immune tolerance among the variety subsets of dendritic cells (DCs) within gut-associated lymphoid tissues (GALTs). Fms-like tyrosine kinase 3 ligand (FLT3L) is involved in the differentiation of DCregs and the subsequent expansion of regulatory T-cells (Tregs) mediated by DCregs, though the precise mechanism remains poorly understood. This study aimed to explore the expansion mechanism of Treg induced by DCreg and the role of FLT3L in this process.
METHODS:
DCregs were distinguished from other DC subsets isolated from GALTs of BALB/c mice through a mixed lymphocyte reaction assay. The functions and mechanisms by which FLT3L promoted Treg expansion via DCregs were investigated in vitro through co-culture experiments involving DCregs and either CD4 + CD25 - T-cells or CD4 + CD25 + T-cells. Additionally, an in vivo experiment was conducted using a dextran sulfate sodium (DSS)-induced colitis model in mice.
RESULTS:
CD103 + CD11b + DC exhibited DCreg-like functionality and was identified as DCreg for subsequent investigation. Analysis of Foxp3 + Treg percentages within a co-culture system of CD4 + CD25 - T-cells and DCregs, with or without FLT3L, demonstrated the involvement of the FLT3/FLT3L axis in driving the differentiation of precursor T-cells into Foxp3 + Tregs induced by DCregs. Cell migration and co-culture assays revealed that the FLT3/FLT3L axis enhanced DCreg migration toward Tregs via the Rho pathway. Additionally, it was observed that DCregs could promote Treg proliferation through the Notch pathway, as inhibition of Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) suppressed Treg expansion within the co-culture system of DCregs and CD4 + T-cells or CD4 + CD25 + T-cells. Furthermore, the FLT3/FLT3L axis influenced JAG1 expression in DCregs, indirectly modulating Treg expansion. In vivo experiments further established that FLT3L promoted DCreg expansion and restored Treg balance in DSS-induced colitis models, thereby ameliorating colitis symptoms in mice.
CONCLUSION
The FLT3/FLT3L axis is integral to the maintenance of DCreg function in Treg expansion.
Animals
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T-Lymphocytes, Regulatory/immunology*
;
Dendritic Cells/immunology*
;
Mice
;
Mice, Inbred BALB C
;
Membrane Proteins/metabolism*
;
Receptors, Notch/metabolism*
;
Lymphoid Tissue/metabolism*
;
Signal Transduction/physiology*
;
Coculture Techniques
;
Flow Cytometry
2.Treatment and prognosis of primary ocular adnexal extranodal marginal zone mucosa-associated lymphoid tissue lymphoma: a report from a single center.
Xin LI ; Jin YE ; Lei YANG ; Li Qiang WEI ; Jia CONG ; Na YAO ; Jing YANG ; Jing Wen WANG
Chinese Journal of Hematology 2022;43(3):209-214
Objective: This study aimed to see how different initial treatment regimens affected the long-term prognosis of patients with extranodal marginal zone mucosa-associated lymphoid tissue lymphoma confining to the ocular adnexal (OAML) . Methods: Between April 2008 and April 2019, 109 patients with initial mucosa-associated lymphoid tissue confining to ocular adnexal were evaluated and followed-up, and the prognosis of various initial treatment regimens were examined. Results: A total of 36 patients underwent complete surgical resection of the lesions, and 73 patients had residual lesions after surgery, of which 37 patients chose watchful waiting, and 36 patients chose treatment. The treatment regimen included local radiotherapy and systemic treatment (chemotherapy, immunochemotherapy, the combination of radiotherapy and chemotherapy, etc.) , and no serious toxic and side effects were observed in patients receiving systemic treatment. The median follow-up time was 61 (10-142) months. The 5-year and 10-year progression-free survival (PFS) of monocular involvement patients were 78.2% and 76.0% . The 5-year and 10-year PFS rates of patients with binocular involvement were 64.4% and 23.5%. There was significant diference in PFS between patients with monocular and binocular involvement (P=0.010) . Patients who received additional treatment had higher PFS than those patients in the watchful waiting group (P=0.046) . The 5-year PFS was 71.4% and 90.1% among patients in the watchful waiting group and those who received additional treatment, whereas the 10-year PFS was 63.5% and 75.1% , respectively. Patients with OAML were still a risk of disease progression after 5 years. Conclusions: Patients with binocular involvement OAML at the start of the disease had a poor prognosis, but treatment could reduce the risk of recurrence/progression. Systemic therapy is one of the first-line treatment options for patients with OAML, who require long-term monitoring.
Eye Neoplasms/radiotherapy*
;
Humans
;
Lymphoid Tissue/pathology*
;
Lymphoma, B-Cell, Marginal Zone/therapy*
;
Prognosis
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Retrospective Studies
;
Treatment Outcome
3.Molecular Characteristics and Clinical Significance of IGH Gene Rearrangement in B-Cell Lymphoma--Review.
Journal of Experimental Hematology 2022;30(4):1291-1295
B-cell lymphoma is the most common malignant lymphoma, and its incidence is increasing year by year. Some types are often indistinguishable from the reactive lesions through morphology combined with immunohistochemistry, so other auxiliary diagnostic methods are urgently needed. Since B-cell lymphoma is caused by malignant transformation of IGH rearranged B cells, the molecular characteristics of rearranged B cells can be used as an important reference for differentiating benign and malignant proliferations of lymphatic tissues. With the development of molecular biology technology, the detection of clonal rearrangement of IGH plays an important role in the diagnosis, efficacy evaluation and prognosis evaluation of lymphoma. This paper focuses on the molecular characteristics and clinical significance of clonal rearrangement of IGH in B-cell lymphoma.
Gene Rearrangement
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Humans
;
Lymphoid Tissue/pathology*
;
Lymphoma
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Lymphoma, B-Cell/genetics*
;
Polymerase Chain Reaction
4.Revision of Laboratory Testing Guidelines for Initial Diagnosis of Hematologic Neoplasms
In Suk KIM ; Ja Young LEE ; Sun Young KONG ; Seung Tae LEE ; Jungwon HUH ; Myung Hyun NAM ; Myungshin KIM ; Young Uk CHO ; Hee Jin HUH ; Jeawoo SONG ; Hyosoon PARK
Laboratory Medicine Online 2020;10(1):10-24
lymphoid tissues. The new guidelines were revised based on an extensive review of international guidelines that included the National Comprehensive Cancer Network Guidelines, and European LeukemiaNet recommendations that are based on the revised WHO classification. We expect that the newly revised guidelines will improve clinical decisions, standardize laboratory tests, and enhance the development of new molecular technologies that are integrated into diagnostic algorithms via ongoing consensus initiatives.]]>
Classification
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Consensus
;
Diagnosis
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Hematologic Neoplasms
;
Hematology
;
Lymphoid Tissue
5.Endoscopic features aiding the diagnosis of gastric mucosa-associated lymphoid tissue lymphoma
Yeungnam University Journal of Medicine 2019;36(2):85-91
The incidence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is increasing worldwide, but the diagnosis is difficult. Most patients are asymptomatic or complain of nonspecific gastrointestinal symptoms. As the endoscopic features of gastric MALT lymphoma are variable and nonspecific, the possibility of this condition may be overlooked during esophagogastroduodenoscopy, and it remain undiagnosed. Therefore, this condition needs to be considered when an abnormal mucosa is observed during this procedure. Biopsy performed during endoscopy is the primary diagnostic test, but false negative results are possible; large numbers of samples should be collected from both normal and abnormal mucosae. Endoscopic ultrasonography is useful to assess the depth of invasion and to predict the treatment response. After treatment, follow-up tests are required every 3 months until complete remission is achieved, and annually thereafter. Early diagnosis of gastric MALT lymphoma is difficult, and its diagnosis and follow-up require wide experience and competent endoscopic technique.
Biopsy
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Diagnosis
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Diagnostic Tests, Routine
;
Early Diagnosis
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Endoscopy
;
Endoscopy, Digestive System
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Endoscopy, Gastrointestinal
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Endosonography
;
Follow-Up Studies
;
Humans
;
Incidence
;
Lymphoid Tissue
;
Lymphoma
;
Lymphoma, B-Cell, Marginal Zone
;
Mucous Membrane
;
Stomach Neoplasms
6.Nodular Gastritis as a Precursor Lesion of Atrophic and Metaplastic Gastritis
Young Jung KIM ; Sun Young LEE ; Hojun YANG ; Jeong Hwan KIM ; In Kyung SUNG ; Hyung Seok PARK
The Korean Journal of Gastroenterology 2019;73(6):332-340
BACKGROUND/AIMS: Chronic atrophic gastritis (CAG) and metaplastic gastritis (MG) are precancerous conditions of Helicobacter pylori (H. pylori)-related gastric cancer. This study aimed to identify the characteristics of nodular gastritis (NG) showing CAG or MG after nodule regression.METHODS: H. pylori-infected patients with NG were included after upper gastrointestinal endoscopy. Patients were excluded if their latest endoscopy had been performed ≤36 months after the initial diagnosis of NG. Small-granular-type NG was defined as the condition with 1–2 mm regular subepithelial nodules. Large-nodular-type NG was defined as those with 3–4 mm, irregular subepithelial nodules. The endoscopic findings after nodule regression were recorded.RESULTS: Among the 97 H. pylori-infected patients with NG, 61 showed nodule regression after a mean follow-up of 73.0±22.0 months. After nodule regression, 16 patients showed a salt-and-pepper appearance and/or transparent submucosal vessels, indicating CAG. Twenty-nine patients showed diffuse irregular elevations and/or whitish plaques, indicating MG. Sixteen patients with other endoscopic findings (14 normal, one erosive gastritis, and one chronic superficial gastritis) showed a higher proportion of H. pylori eradication (12/16, 75.0%) than those in the CAG group (5/16, 31.3%) and MG group (6/29, 20.7%; p=0.001). Patients with small-granular-type NG tended to progress toward CAG (14/27, 51.9%), whereas those with large-nodular-type NG tended to progress toward MG (25/34, 73.5%; p<0.001).CONCLUSIONS: In patients with a persistent H. pylori infection, NG tended to progress to CAG or MG when the nodules regressed. Small-granular-type NG tended to progress to CAG, whereas large-nodular-type NG tended to progress to MG.
Atrophy
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Diagnosis
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Endoscopy
;
Endoscopy, Gastrointestinal
;
Follow-Up Studies
;
Gastritis
;
Gastritis, Atrophic
;
Helicobacter pylori
;
Humans
;
Lymphoid Tissue
;
Metaplasia
;
Precancerous Conditions
;
Stomach Neoplasms
7.A Case report of MALT lymphoma in parotid gland
Myeong Hee KIM ; Jong Joong CHOI ; Hong Geun AHN ; Joong Su PARK ; Yeon Soo KIM
Korean Journal of Head and Neck Oncology 2019;35(1):33-36
Mucosa-associated lymphoid tissue (MALT) lymphoma has specific clinical and pathologic features. The most common site MALT lymphomas is the stomach; however, it can also occur in other organs, such as the salivary glands. MALT lymphoma is rare, but its prognosis is good. A 32-year-old man visited Konyang university hospital with parotid mass. Superficial partial parotidectomy was performed to exclude lymphoid neoplasms. IgH gene rearrangement analysis of the surgical specimen led to the diagnosis of MALT lymphoma. The patient underwent esophagogastroduodenoscopy, positron emission tomography-computed tomography, and whole-body bone scan. Regional or distant metastasis was not observed on staging workup. The patient underwent postoperative radiation therapy, there has been no recurrence of MALT lymphoma to date. Here, we report this rare case of parotid MALT lymphoma that was treated with surgery and postoperative radiation therapy.
Adult
;
Diagnosis
;
Electrons
;
Endoscopy, Digestive System
;
Gene Rearrangement
;
Humans
;
Lymphoid Tissue
;
Lymphoma
;
Lymphoma, B-Cell, Marginal Zone
;
Neoplasm Metastasis
;
Parotid Gland
;
Prognosis
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Recurrence
;
Salivary Glands
;
Stomach
8.Clinical Efficacy of Radiotherapy in Helicobacter pylori Negative or Unresponsive to Eradication Therapy Primary Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.
The Korean Journal of Gastroenterology 2019;73(1):19-25
BACKGROUND/AIMS: The eradication of Helicobacter pylori (H. pylori) is an effective treatment in gastric mucosa-associated lymphoid tissue (MALT) lymphoma associated with H. pylori infection. However, the treatment strategy in gastric MALT lymphoma patients who are H. pylori-negative or unresponsive to H. pylori eradication therapy remains controversial. In this study, we investigated the clinical efficacy of treatments other than H. pylori eradication therapy in these groups of patients. METHODS: This was a retrospective single-center study based on the medical records of patients diagnosed with gastric MALT lymphoma at Yeungnam University Medical Center between January 2005 and December 2016. Patients were treated with H. pylori eradication therapy, chemotherapy, or radiotherapy according to their H. pylori infection status and stage of gastric MALT lymphoma. RESULTS: Of the 68 eligible patients, 50 were enrolled in the study. Of the 42 patients with H. pylori-positive gastric MALT lymphoma, 36 (81.7%) were treated with H. pylori eradication therapy as primary treatment and 25 (69.4%) achieved a complete response (CR). Patients without a CR after H. pylori eradication therapy (n=11, 30.6%) received radiotherapy as a secondary treatment. Two patients with H. pylori-positive gastric MALT lymphoma and eight with H. pylori-negative gastric MALT lymphoma received radiotherapy as the primary treatment. CR was achieved in all 21 patients treated with radiotherapy as primary or secondary treatment. The 5-year progression-free survival rate after radiotherapy was 92.9%. CONCLUSIONS: Radiotherapy may be a worthwhile treatment option in patients with H. pylori-negative MALT lymphoma or H. pylori-positive MALT lymphoma that is not responsive to H. pylori eradication therapy.
Academic Medical Centers
;
Disease-Free Survival
;
Drug Therapy
;
Helicobacter pylori*
;
Helicobacter*
;
Humans
;
Lymphoid Tissue
;
Lymphoma
;
Lymphoma, B-Cell, Marginal Zone*
;
Medical Records
;
Radiotherapy*
;
Retrospective Studies
;
Stomach Neoplasms
;
Treatment Outcome*
9.Primary Lymphoma of Pancreatic Mucosa-Associated Lymphoid Tissue (MALT)
Jiwoo LEE ; So Hye NAM ; Jang Ho LEE ; Dong Ryeol YOO ; Jin Hee KIM ; Mee Jeong KIM ; Myung Hwan KIM
Korean Journal of Medicine 2019;94(5):443-448
Primary lymphoma of pancreatic mucosa-associated lymphoid tissue (MALT) is extremely rare. Initial suspicion of primary pancreatic lymphoma is hampered by its low incidence. However, it should always be included in a differential diagnosis of pancreatic mass with unusual features, because an accurate diagnosis can avoid unnecessary surgical intervention. A 70-year-old woman presented with melena associated with a mass on the pancreatic head. Endoscopic ultrasonography-guided core-needle biopsy of the pancreatic mass revealed MALT lymphoma. The patient is currently undergoing radiation therapy. We present a case of primary lymphoma of the pancreatic MALT with a review of the literature.
Aged
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Biopsy
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Diagnosis
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Diagnosis, Differential
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Female
;
Head
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Humans
;
Incidence
;
Lymphoid Tissue
;
Lymphoma
;
Lymphoma, B-Cell, Marginal Zone
;
Melena
10.Mucosa-associated lymphoid tissue lymphoma on right lower eyelid previously diagnosed as lymphoid hyperplasia
Yang Seok KIM ; Young Cheon NA ; Woo Hoe HUH ; Ji Min KIM
Archives of Craniofacial Surgery 2019;20(1):66-70
Mucosa-associated lymphoid tissue (MALT) lymphoma is an uncommon form of non-Hodgkin lymphoma involving the mucosa-associated lymphoid tissue. Most commonly affected organ is the stomach. But, it could affect almost every organ in the whole body. If they have suspicious lesion, excision biopsy could be made. For staging, blood test including blood smear, abdomen and chest tomography or scan will be checked. Also, bone marrow test can be done if it is needed. The patient had visited the clinic for palpable mass on right lower eyelid. With excisional biopsy, it was diagnosed as lymphoid hyperplasia on pathologic test. But 2 years later, the patient came with recurrent symptom for our department with worry. At that time, we recommended excisional soft tissue biopsy under general anesthesia. Unfortunately, it was revealed MALT lymphoma on pathologic finding. It turned out to be stage 3 in Ann Arbor staging system without B symptoms. Hematologic consultation was made and she was treated with adjuvant chemotherapy for eight cycles to complete remission. We report a case of MALT lymphoma on subcutaneous tissue at right lower eyelid previously diagnosed as lymphoid hyperplasia.
Abdomen
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Anesthesia, General
;
Biopsy
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Bone Marrow
;
Chemotherapy, Adjuvant
;
Eyelids
;
Hematologic Tests
;
Humans
;
Hyperplasia
;
Lymphoid Tissue
;
Lymphoma
;
Lymphoma, B-Cell, Marginal Zone
;
Lymphoma, Non-Hodgkin
;
Stomach
;
Subcutaneous Tissue
;
Thorax

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