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第十届全国免疫学学术大会

作者： Yiping Li Yao He Yang-Xin Fu Xiaohuan Guo Tsinghua University School of Medicine Department of Pathology The University of Chicago

Gut associated lymphoid tissues(GALT),including the mesentery lymph nodes(m LNs),Peyer’s patches(PPs),and isolated lymphoid follicles(ILFs),are important locations for the initiation of adaptive immune responses in the intestine.group 3 innate lymphoid cells(ILC3s)are defined by their expression of RORγt and include lymphoid tissue inducer(LTi)cells,which play a critical role in the development of GALT.Recent studies have shown that Id2 is essential for the development of ILC precursors,however,the function of Id2 in these well-differentiated ILCs is still unclear.To study the function of Id2 in RORγt+ILC3s,Id2 conditional knockout mice(RorccreId2fl/fl)were used.Compared with WT mice,RorccreId2fl/fl mice showed normal LNs,but completely lacked PPs and ILFs,suggesting that Id2 in RORγt+ILC3s is required for the formation of PPs and ILFs,but not LNs.Furthermore,RORγt+ILC3s were significantly reduced in the colon and small intestine of RorccreId2fl/fl mice compared with WT mice.Interestingly,the RORγt+ILC3s were actually increased in m LN in RorccreId2fl/fl than WT mice,indicating that the development or maintenance of RORγt+ILC3s in the gut,but not LNs,required Id2 regulation.Moreover,Id2 deficient LTi cells exhibited significantly reduction of the lymphotoxin expression,which is important for the formation of GALT.Furthermore,we found IL-7 stimulation could induce LT expression in WT ILC3s,while the IL-7Rαexpression was dramatically reduced in Id2 deficient LTi cells,suggesting that Id2 may regulate the lymphotoxin expression through IL-7 signaling.Taken together,our results suggest that Id2 could regulate the function and maintenance of LTi cells through IL-7 signaling to further determine the development of PPs and ILFs.However,how Id2 controls IL-7R and why LTi are differentially regulated in m LN and gut need to be further determined.

关键词： group 3 innate lymphoid cells Id2 lymphotoxin gut associated lymphoid tissue

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Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR+ ILC3

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Chinese Journal of Integrative Medicine 2023年第5期29卷 424-433页

作者： CHEN Ming-jun FENG Yang GAO Lu LIN Ming-xiong WANG Shi-da TONG Zhan-qi Medical School of Chinese People's Liberation Army Beijing(100853)China Department of Traditional Chinese Medicine The Second Medical Center&National Clinical Research Center of Geriatric DiseasesChinese People's Liberation Army General HospitalBeijing(100853)China Institute of Military Cognition and Brain Sciences Academy of Military Medical SciencesAcademy of Military SciencesBeijing(100850)China

Objective: To investigate the effects of composite Sophora colon-soluble Capsule(CSCC) on gut microbiota-mediated short-chain fatty acids(SCFAs) production and downstream group 3 innate lymphoid cells(ILC3s) of dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) mice model. Methods: The main components of CSCC were analyzed by hybrid ultra-high-performance liquid chromatography ion mobility spectromety quadrupole time-of-flight mass spectrometry(UHPLC-IM-QTOF/MS). Twenty-four male BALB/c mice were randomly divided into 4 groups(n=6) by using a computer algorithm-generated random digital, including control, DSS model, mesalazine, and CSCC groups. A DSS-induced colitis mice model was established to determine the effects of CSCC by recording colonic weight, colonic length, index of colonic weight, and histological colonic score. The variations in ILC3s were assessed by immunofluorescence and flow cytometry. The results of gut microbiota and SCFAs were acquired by 16s r DNA and gas chromatography-mass spectrometry(GC-MS) analysis. The expression levels of NCR^(+)ILC3^(-), CCR6^(+)Nkp46-(Lti) ILC3^(-), and ILCreg-specific markers were detected by enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction and Western blot, respectively. Results: The main components of CSCC were matrine, ammothamnine, Sophora flavescens neoalcohol J, and Sophora oxytol U. After 7 days of treatment, CSCC significantly alleviated colitis by promoting the reproduction of intestinal probiotics manifested as upregulation of the abundance of Bacteroidetes species and specifically the Bacteroidales_S24-7 genus(Pgroup, Lti ILC3s and its biomarkers were significantly downregulated and NCR^(+) ILC3s were significantly elevated in the CSCC group(P3s were differentiated from Lti ILC3s to NCR^(+)ILC3s, resulting in interleukin-22 production wh

关键词： composite Sophora colon-soluble capsule ulcerative colitis group 3 innate lymphoid cells gut microbiota butyric acid

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ILC3-derived OX40L is essential for homeostasis of intestinal Tregs in immunodeficient mice

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Cellular & Molecular Immunology 2020年第2期17卷 163-177页

作者： Tian Deng Caixia Suo Jiali Chang Rui Yang Jingyu Li Ting Cai Ju Qiu CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Jiao Tong University School of Medicine(SJTUSM)&Shanghai Institutes for Biological Sciences(SIBS)Chinese Academy of Sciences(CAS)Shanghai 200031China CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institutes for Biological SciencesUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China

OX40L is one of the co-stimulatory molecules that can be expressed by splenic lymphoid tissue inducer(Lti)cells,a subset of group 3 innate lymphoid cells(ILC3s).OX40L expression in subsets of intestinal ILC3s and the molecular regulation of OX40L expression in ILC3s are unknown.Here,we showed intestinal ILC3s marked as an OX40L high population among all the intestinal leukocytes and were the dominant source of OX40L in Rag1–/–mice.All ILC3 subsets expressed OX40L,and NCR–ILC3s were the most abundant source of OX40L.The expression of OX40L in ILC3s could be upregulated during inflammation.In addition to tumor necrosis factor(TNF)-like cytokine 1A(TL1A),which has been known as a trigger for OX40L,we found that Poly(I:C)representing viral stimulus promoted OX40L expression in ILC3s via a cell-autonomous manner.Furthermore,we demonstrated that IL-7-STAT5 signaling sustained OX40L expression by ILC3s.Intestinal regulatory T cells(Tregs),most of which expressed OX40,had defective expansion in chimeric mice,in which ILC3s were specifically deficient for OX40L expression.Consistently,co-localization of Tregs and ILC3s was found in the cryptopatches of the intestine,which suggests the close interaction between ILC3s and Tregs.Our study has unveiled the crosstalk between Tregs and ILC3s in mucosal tissues through OX40–OX40L signaling,which is crucial for the homeostasis of intestinal Tregs.

关键词： group 3 innate lymphoid cells OX40L Regulatory T cells Intestinal immunity

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Obesity may provide a pro ILC3s development inflammatory environment in asthmatic

Obesity may provide a pro ILC3s development inflammatory env...

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第十三届全国免疫学学术大会

作者： Yumin Wu THE FIRST PEOPLR’S HOSPITAL OF CHANGZHOU

The prevalence of obesity in children has dramatically increased in the last few decades, and obesity has also emerged as an important risk factor for asthma.innate mechanisms have been shown to be involved in both diseases, particularly through the recently described innate lymphoid cells(ILCs), in which ILC3s have been linked to obesity both in human and in murine models.The aim of this study was to explore whether being overweight in asthmatic children was associated with elevated circulating ILC3 or elevated messenger RNA(mRNA)-levels of RORC, IL-17A and IL-22.Our results showed significantly elevated ILC3 frequencies in overweight asthmatic children compared with non-overweight controls based on the detection of Lin+CD127IL-23R cells by flow cytometry.Moreover, elevated ILC3 frequencies positively correlated with the mRNA expression of RORC which has been identified as a transcription factor of ILC3s.The relative mRNA expression level of IL-17A was also upregulated in overweight compared to non-overweight children, as was the relative mRNA level of IL-22.However, there were no correlations between ILC3s frequencies or the expression of, RORC, IL-17A and IL-22 and asthma severity.These results suggested that childhood obesity is an independent factor that is associated with an elevated frequency of circulating ILC3s and higher expression of RORC, IL-22 and IL-17A.

关键词： Obesity Asthma group 3 innate lymphoid cells IL-17A

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