Reg4 and complement factor D prevent the overgrowth of E. coli in the mouse gut

Qi, Houbao; Wei, Jianmei; Gao, Yuan; Yang, Yazheng; Li, Yuanyuan; Zhu, Hua; Su, Lei; Su, Xiaomin; Zhang, Yuan; Yang, Rongcun

doi:10.1038/s42003-020-01219-2

Cited by 31 publications

(27 citation statements)

References 62 publications

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“…In contrast to Reg III, Reg IV is produced predominantly by deep crypt secretory cells and intestinal enteroendocrine cells in the colon [55]. Gut Reg IV-and complement factor D-mediated membrane attack complexes may help to maintain gut homeostasis by elimination of inflammatory E. coli [56].…”

Section: Reg and Inflammatory Diseases (Gi Tract And Systemic Inflammation)mentioning

confidence: 99%

The Potential Role of REG Family Proteins in Inflammatory and Inflammation-Associated Diseases of the Gastrointestinal Tract

Sun

Wang

Hui

et al. 2021

IJMS

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Regenerating gene (REG) family proteins serve as multifunctional secretory molecules with trophic, antiapoptotic, anti-inflammatory, antimicrobial and probably immuno-regulatory effects. Since their discovery, accumulating evidence has clarified the potential roles of the REG family in the occurrence, progression and development of a wide range of inflammatory and inflammation-associated diseases of the gastrointestinal (GI) tract. However, significant gaps still exist due to the undefined nature of certain receptors, regulatory signaling pathways and possible interactions among distinct Reg members. In this narrative review, we first describe the structural features, distribution pattern and purported regulatory mechanisms of REG family proteins. Furthermore, we summarize the established and proposed roles of REG proteins in the pathogenesis of various inflammation-associated pathologies of the GI tract and the body as a whole, focusing particularly on carcinogenesis in the ulcerative colitis—colitic cancer sequence and gastric cancer. Finally, the clinical relevance of REG products in the context of diagnosis, treatment and prognostication are also discussed in detail. The current evidence suggests a need to better understanding the versatile roles of Reg family proteins in the pathogenesis of inflammatory-associated diseases, and their broadened future usage as therapeutic targets and prognostic biomarkers is anticipated.

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Section: Reg and Inflammatory Diseases (Gi Tract And Systemic Inflammation)mentioning

confidence: 99%

The Potential Role of REG Family Proteins in Inflammatory and Inflammation-Associated Diseases of the Gastrointestinal Tract

Sun

Wang

Hui

et al. 2021

IJMS

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“…In addition, enteropathogenic Escherichia coli also can activate NLRC4 21 . While equal amount of GFP-labeled Escherichia coli, which were isolated from DSS-mediated colitis and demonstrated to promote in ammation 27 , both LNCGM1082-/and NLRC4-/mice had also similarly increased bacteria as compared to wt mice in the feces after 2 days (Fig. 3i).…”

Section: Lncgm1082 Has Similar Effects With Nlrc4 On Regulating Maturation Of Il-1β and Pyroptosis Of Macrophagesmentioning

confidence: 99%

NLRC4 activation needs lncRNA LNCGM1082

Gao

Yang

Wei

et al. 2021

Preprint

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The activation of NLRC4 is a major host response against the infection by intracellular bacteria. However, there still remain challenges in understanding the activation upon sensing of diverse stimuli. We here found that lncRNA LNCGM1082 plays a critical role in the activation of NLRC4. LNCGM1082 in macrophages could affect maturation of interleukin (IL)-1β and pyroptotic cell death only after exposed to NLRC4 ligand. Similar to NLRC4-/- mice, LNCGM1082-/- mice were high sensitive to Salmonella typhimurium infection. LNCGM1082 deficiency in mouse or human macrophages had reduced IL-1β maturation and pyroptosis. Mechanistically, LNCGM1082 could induce the combination of PKCδ with NLRC4 in both mice and human. There was absence of binding of NLRC4 with PKCδ in LNCGM1082-/- macrophages. This lncRNA could be induced by Salmonella typhimurium through TLR5 in the macrophages of both mice and human. Thus, our data indicate that LNCGM1082 induced by TLR5 can mediate the binding of PKCδ with NLRC4 to cause the activation of NLRC4.

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“…We previously reported that Reg4 could kill E. coli through complement-dependent pathway [35]. Since increased E. coli in colon are related to occurrence and development of multiple diseases such as obesity [36-38], we investigated the role of Reg4 in high-fat diet (HFD) mediated obesity using Reg4 knockout (KO) mice.…”

Section: Reg4 Promotes Resistance To High-fat Diet Induced Obesitymentioning

confidence: 99%

“…Reg4 associated gut microbiota/metabolites are related to IL-35 + cells Gut microbiota /metabolites play a critical role in the formation of immune system [1][2][3]. Reg4 can not only kill E. coli through complement-dependent pathway [35] but also induce damage to bacterial cell wall [33,34], implying that Reg4 might cause changed gut microbiota in gut. Indeed, ow cytometry showed that WGA + bacteria increased but LPS + bacteria reduced in the fresh stool of huREG4 IECtg mice; whereas WGA + bacteria decreased but LPS + bacteria increased in Reg4 KO mice as compared to their control (Fig.…”

Section: Reg4 Promotes Resistance To High-fat Diet Induced Obesitymentioning

confidence: 99%

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Gut microbiota derived metabolites 3-idoleacetic acid with LPS induces generation of IL-35+B cells

Yang¹,

Su²,

Qi³

et al. 2021

Preprint

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Background IL-35 producing B and Treg cells are critical regulators in worldwide chronic illnesses, which are related to disruptions of gut microbiota composition. Whether gut microbiota regulate these IL-35+ cells maintains elusive. Here we investigated the regulation of gut microbiota in the IL-35+ cells through genetically modified mouse models against obesity. Results Here, we first found that gut Reg4 can promote resistance to high-fat diet induced obesity. Using 16S rRNA gene-based microbiota analysis combined with LC-MS (Liquid chromatography-mass spectrometry)/MS, we demonstrate that gut Reg4 associated microbiota such as lactobacillus can promote generation of the IL-35+ B cells through producing 3-idoleacetic acid (IAA) in the presence of LPS. HuREG4IECtg mice had accumulation of IL-35+ cells not only in adipose but also in colon after feeding high-fat diet; whereas decreased IL-35+ cells in adipose and colon tissues could be detected in Reg4 knockout (KO) mice. Lower levels of IAA were also detected in the peripheral blood of individuals with obesity. Mechanistically, IAA with LPS mediated IL35+ B cells are through PXR and TLR4. PXR KO or TLR4 KO impaired generation of IL-35+B cells. Conclusion IAA with LPS can induce generation of the IL-35+B cells through PXR and TLR4.

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Reg4 and complement factor D prevent the overgrowth of E. coli in the mouse gut

Cited by 31 publications

References 62 publications

The Potential Role of REG Family Proteins in Inflammatory and Inflammation-Associated Diseases of the Gastrointestinal Tract

The Potential Role of REG Family Proteins in Inflammatory and Inflammation-Associated Diseases of the Gastrointestinal Tract

NLRC4 activation needs lncRNA LNCGM1082

Gut microbiota derived metabolites 3-idoleacetic acid with LPS induces generation of IL-35+B cells

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