LKB1 regulates ILC3 postnatal development and effector function through metabolic programming
IntroductionGroup 3 Innate Lymphoid Cells (ILC3s) are important for maintaining intestinal homeostasis and host defense. Emerging studies have shown that metabolic regulation plays a crucial role in regulating ILC3 activation and function. However, the role of Liver Kinase B1 (LKB1), a key metabolic...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1587256/full |
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| author | Huasheng Zhang Huasheng Zhang Huasheng Zhang Linfeng Zhao Linfeng Zhao Linfeng Zhao Qingbing Zhang Qingbing Zhang Qingbing Zhang Lin Hu Lin Hu Lin Hu Xiaohui Su Xiaohui Su Xiaohui Su Jiping Sun Jiping Sun Jiping Sun Lei Shen Lei Shen Lei Shen |
| author_facet | Huasheng Zhang Huasheng Zhang Huasheng Zhang Linfeng Zhao Linfeng Zhao Linfeng Zhao Qingbing Zhang Qingbing Zhang Qingbing Zhang Lin Hu Lin Hu Lin Hu Xiaohui Su Xiaohui Su Xiaohui Su Jiping Sun Jiping Sun Jiping Sun Lei Shen Lei Shen Lei Shen |
| author_sort | Huasheng Zhang |
| collection | DOAJ |
| description | IntroductionGroup 3 Innate Lymphoid Cells (ILC3s) are important for maintaining intestinal homeostasis and host defense. Emerging studies have shown that metabolic regulation plays a crucial role in regulating ILC3 activation and function. However, the role of Liver Kinase B1 (LKB1), a key metabolic regulator, in regulating ILC3 function and intestinal immunity remains poorly understood.MethodsTo investigate the role of LKB1 in intestinal ILC3s, we generated LKB1 conditional knockout mice by crossing Rorccre and Stk11flox/flox mice. Cell number and cytokine production was examined using flow cytometry. Citrobacter rodentium infection model were used to determine the role of LKB1 in intestinal defense. RT-qPCR, flow cytometry and immunohistochemistry were used to assess the intestinal inflammatory responses.ResultsIn this study, we show that LKB1 is essential for ILC3 postnatal development, effector function, and intestinal immunity. LKB1-deficient mice exhibit a marked decrease in ILC3 number at 2 -3 weeks after birth. Ablation of LKB1 in ILC3s results in diminished IL-22 production and less protection against Citrobacter rodentium infection. Moreover, LKB1 deficiency leads to impaired cell metabolism, as indicated by reduced glycolysis and oxidative phosphorylation and less mitochondrial mass. Together, our data demonstrate that LKB1 promotes ILC3 postnatal development and effector function to maintain intestinal immune homeostasis.DiscussionOur findings reveal that LKB1 is a key regulator of intestinal ILC3 development, function, and metabolism, thereby linking metabolic control to intestinal immune homeostasis and offering potential therapeutic implications. |
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| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-d9672bc47fa04cb49d28a65c6d0b52542025-08-20T03:24:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15872561587256LKB1 regulates ILC3 postnatal development and effector function through metabolic programmingHuasheng Zhang0Huasheng Zhang1Huasheng Zhang2Linfeng Zhao3Linfeng Zhao4Linfeng Zhao5Qingbing Zhang6Qingbing Zhang7Qingbing Zhang8Lin Hu9Lin Hu10Lin Hu11Xiaohui Su12Xiaohui Su13Xiaohui Su14Jiping Sun15Jiping Sun16Jiping Sun17Lei Shen18Lei Shen19Lei Shen20Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCenter for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCenter for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCenter for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCenter for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCenter for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCenter for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaIntroductionGroup 3 Innate Lymphoid Cells (ILC3s) are important for maintaining intestinal homeostasis and host defense. Emerging studies have shown that metabolic regulation plays a crucial role in regulating ILC3 activation and function. However, the role of Liver Kinase B1 (LKB1), a key metabolic regulator, in regulating ILC3 function and intestinal immunity remains poorly understood.MethodsTo investigate the role of LKB1 in intestinal ILC3s, we generated LKB1 conditional knockout mice by crossing Rorccre and Stk11flox/flox mice. Cell number and cytokine production was examined using flow cytometry. Citrobacter rodentium infection model were used to determine the role of LKB1 in intestinal defense. RT-qPCR, flow cytometry and immunohistochemistry were used to assess the intestinal inflammatory responses.ResultsIn this study, we show that LKB1 is essential for ILC3 postnatal development, effector function, and intestinal immunity. LKB1-deficient mice exhibit a marked decrease in ILC3 number at 2 -3 weeks after birth. Ablation of LKB1 in ILC3s results in diminished IL-22 production and less protection against Citrobacter rodentium infection. Moreover, LKB1 deficiency leads to impaired cell metabolism, as indicated by reduced glycolysis and oxidative phosphorylation and less mitochondrial mass. Together, our data demonstrate that LKB1 promotes ILC3 postnatal development and effector function to maintain intestinal immune homeostasis.DiscussionOur findings reveal that LKB1 is a key regulator of intestinal ILC3 development, function, and metabolism, thereby linking metabolic control to intestinal immune homeostasis and offering potential therapeutic implications.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1587256/fullgroup 3 innate lymphoid cells (ILC3s)Liver Kinase B1 (LKB1)metabolic programmingintestinal immune homeostasisinflammation |
| spellingShingle | Huasheng Zhang Huasheng Zhang Huasheng Zhang Linfeng Zhao Linfeng Zhao Linfeng Zhao Qingbing Zhang Qingbing Zhang Qingbing Zhang Lin Hu Lin Hu Lin Hu Xiaohui Su Xiaohui Su Xiaohui Su Jiping Sun Jiping Sun Jiping Sun Lei Shen Lei Shen Lei Shen LKB1 regulates ILC3 postnatal development and effector function through metabolic programming Frontiers in Immunology group 3 innate lymphoid cells (ILC3s) Liver Kinase B1 (LKB1) metabolic programming intestinal immune homeostasis inflammation |
| title | LKB1 regulates ILC3 postnatal development and effector function through metabolic programming |
| title_full | LKB1 regulates ILC3 postnatal development and effector function through metabolic programming |
| title_fullStr | LKB1 regulates ILC3 postnatal development and effector function through metabolic programming |
| title_full_unstemmed | LKB1 regulates ILC3 postnatal development and effector function through metabolic programming |
| title_short | LKB1 regulates ILC3 postnatal development and effector function through metabolic programming |
| title_sort | lkb1 regulates ilc3 postnatal development and effector function through metabolic programming |
| topic | group 3 innate lymphoid cells (ILC3s) Liver Kinase B1 (LKB1) metabolic programming intestinal immune homeostasis inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1587256/full |
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