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Characteristics and distinct prognostic determinants of individuals with hepatosplenic T-cell lymphoma over the past two decades

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World Journal of Clinical Oncology 2024年第6期15卷 745-754页

作者： Ayrton Bangolo Pierre Fwelo Shraboni Dey Tanni Sethi Sowmya Sagireddy Jawaria Chatta Ashish Goel Sneha Nagpaul Eric Pin-Shiuan Chen Chiranjeeve Saravanan Sheeja Gangan Joel Thomas Sarah Potiguara Vignesh K Nagesh Daniel Elias Charlene Mansour Prajakta H Ratnaparkhi Priyanshu Jain Midhun Mathew Taylor Porter Shadiya Sultan Shailaja Abbisetty Linh Tran Megha Chawla Abraham Lo Simcha Weissman Christina Cho department of Internal Medicine Palisades Medical CenterNorth BergenNJ 07047United States department of Epidemiology Human Geneticsand Environmental SciencesUTHealth School of Public HealthHoustonTX 77030United States department of Medicine Palisades Medical CenterNorth BergenNJ 07047United States stem cell Transplantation and cellular Therapy John Theurer Cancer CenterHackensackNJ 07601United States

BACKGROUND Hepatosplenic T-cell lymphoma(HSTCL)is a rare and aggressive peripheral T-cell lymphoma with historically dismal outcomes,representing less than one percent of non-Hodgkin *** its rarity,the true incidence of HSTCL is unknown and most data have been extrapolated through case *** the best of our knowledge,the largest and most up to date study addressing the epidemiology and outcomes of patients with HSTCL in the United States covered a period from 1996 to 2014,with a sample size of 122 *** To paint the most updated epidemiological picture of *** A total of 186 patients diagnosed with HSTCL,between 2000 and 2017,were ultimately enrolled in our study by retrieving data from the Surveillance,Epidemiology,and End Results *** analyzed demographics,clinical characteristics,and overall mortality(OM)as well as cancer-specific mortality(CSM)of *** with a P value<0.01 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors,with a hazard ratio of greater than 1 representing adverse prog-nostic *** Overall,the outlook for this rare malignancy is very *** this retrospective cohort study of the United States population,non-Hispanic blacks and the elderly had a higher *** data highlights the need for larger prospective studies to investigate factors associated with worse prognosis in one ethnic group,such as treatment delays,which have been shown to increase mortality in this racial/ethnic group for other cancers.

关键词： Extra nodal lymphoma Mortality Survival Racial disparity Age

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Against all odds:The road to success in the development of human immune reconstitution mice

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Animal Models and Experimental Medicine 2024年第4期7卷 460-470页

作者： Yixiao Bin Jing Ren Haowei Zhang Tianjiao Zhang Peijuan Liu Zhiqian Xin Haijiao Yang Zhuan Feng Zhinan Chen Hai Zhang School of Basic Medical Sciences Shaanxi University of Chinese MedicineXianyangChina department of cell biology National Translational Science Center for Molecular MedicineFourth Military Medical UniversityXi'anChina State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases Fourth Military Medical UniversityXi'anChina department of Occupational&Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment School of Public HealthFourth Military Medical UniversityXi'anChina

The mouse genome has a high degree of homology with the human genome,and its physiological,biochemical,and developmental regulation mechanisms are similar to those of humans;therefore,mice are widely used as experimental ***,it is undeniable that interspecies differences between humans and mice can lead to experimental *** differences in the immune system have become an impor-tant factor limiting current immunological *** application of immunodefi-cient mice provides a possible solution to these *** transplanting human immune cells or tissues,such as peripheral blood mononuclear cells or hematopoietic stem cells,into immunodeficient mice,a human immune system can be reconstituted in the mouse body,and the engrafted immune cells can elicit human-specific immune *** have been actively exploring the development and differen-tiation conditions of host recipient animals and grafts in order to achieve better im-mune *** genetic engineering methods,immunodeficient mice can be further modified to provide a favorable developmental and differentiation microenvironment for the *** initially only being able to reconstruct single T lymphocyte lineages,it is now possible to reconstruct lymphoid and myeloid cells,providing important research tools for immunology-related *** this review,we compare the differences in immune systems of humans and mice,describe the devel-opment history of human immune reconstitution from the perspectives of immuno-deficient mice and grafts,and discuss the latest advances in enhancing the efficiency of human immune cell reconstitution,aiming to provide important references for im-munological related researches.

关键词： hematopoietic stem cell human immune reconstitution immune response immunodeficient mice peripheral blood mononuclear cell transplantation

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EBV-associated lymphoproliferative disease post-CAR-T cell therapy

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Frontiers of Medicine 2024年第2期18卷 394-398页

作者： Shiyuan Zhang Xiaoxi Zhou Shangkun Zhang Na Wang Tongcun Zhang Donghua Zhang Qilin Ao Yang Cao Liang Huang department of Hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Immunotherapy Research center for Hematologic Diseases of Hubei Province Wuhan430030China Institute of biology and Medicine College of Life and Health SciencesWuhan University of Science and TechnologyWuhan430081China department of Pathology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin300020China Tianjin Institutes of Health Science Tianjin301600China

Epstein–Barr virus(EBV)-associated lymphoproliferative diseases(EBV-LPDs)are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation(HSCT).However,their occurrence and treatment post-chimeric antigen receptor-modified T(CAR-T)cell therapy has not been *** patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of *** receiving CAR-T cell therapy in tandem with autologous HSCT,the patients achieved complete ***,with a median time of 38.5 months after CAR-T cell therapy,B-cell-derived EBV-LPDs were diagnosed,and they were relieved through the administration of immune checkpoint inhibitor or B-cell-depleting ***,our report suggests that EBV-LPDs may represent a long-term adverse event after CAR-T cell therapy,especially in patients who previously had EBV-positive disorders,and they can be resolved by immune normalization strategy or B-cell depleting therapy.

关键词： EBV-associated lymphoproliferative disease chimeric antigen receptor T-cell autologous stem cell transplantation immune checkpoint inhibitor

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Development of Chinese herbal medicine for sensorineural hearing loss

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Acta Pharmaceutica Sinica B 2024年第2期14卷 455-467页

作者： Yunhao Wu Jingwen Zhang Qiuping Liu Zhuang Miao Renjie Chai Wenyong Chen State Key Laboratory of Bioelectronics Department of Otolaryngology Head and Neck SurgeryZhongda HospitalSchool of Life Sciences and TechnologyAdvanced Institute for Life and HealthJiangsu Province HighTech Key Laboratory for Bio-Medical ResearchSoutheast UniversityNanjing 210096China department of Otolaryngology-Head and Neck the Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China department of Otolaryngology-Head and Neck Surgery Affiliated Hospital of Jiangnan UniversityWuxi 214000China department of Otolaryngology Head and Neck Surgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610000China Co-Innovation center of Neuroregeneration Nantong UniversityNantong 226001China Institute for stem cell and Regeneration Chinese Academy of ScienceBeijing 100085China Beijing Key Laboratory of Neural Regeneration and Repair Capital Medical UniversityBeijing 100069China

According to the World Health Organization’s world report on hearing,nearly 2.5 billion people worldwide will suffer from hearing loss by 2050,which may contribute to a severe impact on individual life quality and national *** hearing loss(SNHL)occurs commonly as a result of noise exposure,aging,and ototoxic drugs,and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear,which is mainly triggered by reactive oxygen species accumulation,inflammation,and mitochondrial *** recent advances have been made in understanding the ability of cochlear repair and regeneration,there are still no effective therapeutic drugs for *** herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western *** we present trends in research for Chinese herbal medicine for the treatment of SNHL,and elucidate their molecular mechanisms of action,to pave the way for further research and development of novel effective drugs in this field.

关键词： Sensorineural hearing loss Chinese herbal medicine Molecular mechanism Active ingredients Prescriptions Ototoxic drugs Noise Hair cells

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Enhancing immunotherapy efficacy against MHC-I deficient triple-negative breast cancer using LCL161-loaded macrophage membranedecorated nanoparticles

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3218-3231页

作者： Wen Zhang Yihui Zhai Ying Cai Xiang Gong Yunxuan Jiang Rong Rong Chao Zheng Binyu Zhu Helen He Zhu Hao Wang Yaping Li Pengcheng Zhang China State Institute of Pharmaceutical Industry Shanghai 201203China State Key Laboratory of Drug Research&center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Biomedical Engineering&State Key Laboratory of Advanced Medical Materials and Devices ShanghaiTech UniversityShanghai 201210China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China Yantai Institute of Materia Medica Shandong 264000China State Key Laboratory of Oncogenes and Related Genes Renji-Med-X Stem Cell Research CenterDepartment of UrologyRen Ji HospitalSchool of Medicine and School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200127China University of Chinese Academy of Sciences Beijing 100049China

Current cytotoxic T lymphocyte(CTL)activating immunotherapy requires a major histocompatibility complex I(MHC-I)-mediated presentation of tumor-associated antigens,which malfunctions in around half of patients with triple-negative breast cancer(TNBC).Here,we create a LCL161-loaded macrophage membrane decorated nanoparticle(LMN)for immunotherapy of MHC-I-deficient *** on the macrophage membrane helps LMNs recognize CD47-expressing cancer cells for targeted delivery of LCL161,which induces the release of high mobility group protein 1 and proinflammatory cytokines from cancer *** released cytokines and high mobility group protein 1 activate antitumor immunity by increasing the intratumoral density of the phagocytic macrophage subtype by 15 times and elevating the intratumoral concentration of CTL lymphotoxin by 4.6 *** also block CD47-mediated phagocytosis *** inhibit the growth of MHC-I-deficient TNBC tumors,as well as those resistant to combined therapy of anti-PDL1 antibody and albumin-bound paclitaxel,and prolong the survival of animals,during which process CTLs also play important *** macrophage membrane-decorated nanoparticle presents a generalizable platform for increasing macrophagemediated antitumor immunity for effective immunotherapy of MHC-I-deficient cancers.

关键词： MHC-I deficiency Macrophage CD47 Immunotherapy Triple-negative breast cancer Phagocytosis Immune checkpoint Innate immunity

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Expansion of human umbilical cord derived mesenchymal stem cells in regenerative medicine

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World Journal of stem cells 2024年第4期16卷 410-433页

作者： Shafiqa Naeem Rajput Bushra Kiran Naeem Anwar Ali Asmat Salim Irfan Khan Dr.Panjwani center for Molecular Medicine and Drug Research International Center for Chemical and Biological SciencesUniversity of KarachiKarachi 75270SindhPakistan Surgical Unit 4 Dr.Ruth KM Pfau Civil HospitalKarachi 74400Pakistan department of Physiology University of KarachiKarachi 75270Pakistan center for Regenerative Medicine and stem cells Research and Department of Ophthalmology and Visual SciencesThe Aga Khan UniversityKarachi 74800SindhPakistan

BACKGROUND stem cells are undifferentiated cells that possess the potential for self-renewal with the capacity to differentiate into multiple *** humans,their limited numbers pose a challenge in fulfilling the necessary demands for the regeneration and repair of damaged tissues or *** suggested that mesenchymal stem cells(MSCs),necessary for repair and regeneration via transplantation,require doses ranging from 10 to 400 million ***,the limited expansion of MSCs restricts their therapeutic *** To optimize a novel protocol to achieve qualitative and quantitative expansion of MSCs to reach the targeted number of cells for cellular transplantation and minimize the limitations in stem cell therapy *** Human umbilical cord(hUC)tissue derived MSCs were obtained and *** cultured cells were subjected to the following evaluation pro-cedures:Immunophenotyping,immunocytochemical staining,trilineage differentiation,population doubling time and number,gene expression markers for proliferation,cell cycle progression,senescence-associatedβ-galactosidase assay,human telomerase reverse transcriptase(hTERT)expression,mycoplasma,cytomegalovirus and endotoxin *** Analysis of pluripotent gene markers Oct4,Sox2,and Nanog in recultured hUC-MSC revealed no significant *** immunophenotypic markers CD90,CD73,CD105,CD44,vimentin,CD29,Stro-1,and Lin28 were positively expressed by these recultured expanded MSCs,and were found negative for CD34,CD11b,CD19,CD45,and *** recultured hUC-MSC population continued to expand through passage *** gene expression of Pax6,BMP2,and TGFb1 showed no significant variation between recultured hUC-MSC ***,a significant increase(Pcell cycle was observed in recultured *** senescence markers(hTERT expression andβ-galactosidase activity)did not show any negative effect on recultured hUC-

关键词： Human umbilical cord Mesenchymal stem cells Expansion cell proliferation In vitro expansion Senescence

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Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical Medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke Jacqueline Proszynski Braden Tierney Caleb M.Schmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox Christopher Chin Deena Najjar Irina Matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian C.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane C.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus Christopher E.Mason department of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA department of stem cell biology and Regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer Cancer center Weill Cornell MedicineNew YorkNY 10065USA department of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA cell and Molecular biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA Meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic *** advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation *** To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA *** length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational *** Telomere elongation occurred during spaceflight and shortened after return to ***-free DNA analysis revealed increased immune cell signatures *** significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was *** long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career *** study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

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SARS-CoV2 Nsp3 protein triggers cell death and exacerbates amyloid β42-mediated neurodegeneration

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Neural Regeneration Research 2024年第6期19卷 1385-1392页

作者： Aditi Singh Anuradha Venkatakrishnan Chimata Prajakta Deshpande Soumya Bajpai Anjali Sangeeth Mrigendra Rajput Amit Singh department of biology University of DaytonDaytonOHUSA Premedical Program University of DaytonDaytonOHUSA center for Tissue Regeneration and Engineering at Dayton(TREND) University of DaytonDaytonOHUSA The Integrative Science and Engineering center University of DaytonDaytonOHUSA center for Genomic Advocacy(TCGA) Indiana State UniversityTerre HauteINUSA

Infection caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV2)virus,responsible for the coronavirus disease 2019(COVID-19)pandemic,induces symptoms including increased inflammatory response,severe acute respiratory syndrome(SARS),cognitive dysfunction like brain fog,and cardiovascular ***-term effects of SARS-CoV2 COVID-19 syndrome referred to as post-COVID-19 syndrome on age-related progressive neurodegenerative disorders such as Alzheimer's disease remain *** the targeted misexpression of individual SARS-CoV2 proteins in the retinal neurons of the Drosophila melanogaster eye,we found that misexpression of nonstructural protein 3(Nsp3),a papain-like protease,ablates the eye and generates dark necrotic *** misexpression of Nsp3 in the eye triggers reactive oxygen species production and leads to apoptosis as shown by cell death reporters,terminal deoxynucleotidyl transferase(TdT)dUTP Nick-end labeling(TUNEL)assay,and dihydroethidium ***,Nsp3 misexpression activates both apoptosis and autophagy mechanism(s)to regulate tissue *** expression of SARS-CoV2 Nsp3 in murine neuroblastoma,Neuro-2a cells,significantly reduced the metabolic activity of these cells and triggers cell *** of SARS-CoV2 Nsp3 in an Alzheimer's disease transgenic fly eye model(glass multiple repeats[GMR]>amyloidβ42)further enhances the neurodegenerative rough eye phenotype due to increased cell *** findings suggest that SARS-CoV2 utilizes Nsp3 protein to potentiate cell death response in a neurodegenerative disease background that has high pre-existing levels of neuroinflammation and cell death.

关键词： Alzheimer's disease apoptosis autophagy COVID-19 Drosophila necrosis Neuro-2a cells neurodegeneration post COVID-19 syndrome SARS-CoV2

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Mesenchymal stem cell-based TRAIL delivery inhibits the metastatic state of clinical therapy-resistant progressive neuroblastoma

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World Journal of Pediatrics 2024年第3期20卷 287-293页

作者： Dinesh Babu Somasundaram Andrew Maher Sheeja Aravindan Zhongxin Yu Brian MBesch Natarajan Aravindan department of Radiation Oncology University of Oklahoma Health Sciences CenterOklahoma CityOKUSA Stephenson Cancer center Oklahoma CityOKUSA department of Pathology University of Oklahoma Health Sciences CenterOklahoma CityOKUSA Radiation biology Laboratory University of Oklahoma Health Sciences CenterBSEB 302F941 Stanton L.Young BoulevardOklahoma CityOK 73104USA

Progressive neuroblastomas(pNBs)that defy current intensive multimodal clinical therapy(IMCT)are a significant contributor to overall childhood cancer deaths[l].Neuroblastomas(NBs)that survive first-line IMCT actively evolve to acquire genetic and molecular rearrangements and display unparalleled plasticity and evolution,which causes frequent relapses in a rapidly accelerating timeline[2-4].

关键词： neuroblastoma clinical evolve

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Crohn’s disease as the intestinal manifestation of pan-lymphatic dysfunction:An exploratory proposal based on basic and clinical data

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World Journal of Gastroenterology 2024年第1期30卷 34-49页

作者： Yu-Wei Zhou Yue Ren Miao-Miao Lu Ling-Ling Xu Wei-Xin Cheng Meng-Meng Zhang Lin-Ping Ding Dong Chen Jian-Guo Gao Juan Du Ci-Liang Jin Chun-Xiao Chen Yun-Fei Li Tao Cheng Peng-Lei Jiang Yi-Da Yang Peng-Xu Qian Peng-Fei Xu Xi Jin department of Gastroenterology The First Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina department of Gastroenterology The Second Hospital of JiaxingJiaxing 314000Zhejiang ProvinceChina Endoscopy center Children’s Hospital of Zhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina department of Gastroenterology The Second People’s Hospital of Yuhang DistrictHangzhou 310000Zhejiang ProvinceChina department of Gastroenterology Hangzhou Shangcheng District People’s HospitalHangzhou 310003Zhejiang ProvinceChina department of Colorectal Surgery The First Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina department of Gastroenterology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Women’s Hospital and Institute of Genetics Zhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina center of stem cell and Regenerative Medicine and Bone Marrow Transplantation CenterThe First Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina department of Infectious Disease The First Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

Crohn’s disease(CD)is caused by immune,environmental,and genetic *** can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains *** biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known *** achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost *** this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary *** supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid *** benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic *** importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.

关键词： Inflammatory bowel disease Crohn’s disease Lymphatic system Inside-out model Immune cells Zebrafish

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