Lets connect: A novel role for CD46 in tight junction regulation

Al-Shouli, Samia T.; Cardone, John; Sacks, Steven; Kemper, Claudia

doi:10.1016/j.molimm.2010.05.166

Cited by 2 publications

(5 citation statements)

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“…This observation is in line with a recent finding that CD46 participates in the regulation of epithelial cell growth and wound healing by modulating tight junction formation [42]. Further, pathogenic E. coli take advantage of this housekeeping function of CD46 on gut epithelium and induce a dramatic decrease in transepithelial resistance in conjunction with an increase of bacterial paramigration after their binding to CD46 [42]. Interestingly, CD46 engagement by MV and group A streptococci also triggers CD46‐mediated cell autophagy and increased death of infected cells: an elegant example of the host's measures to counteract pathogen abuse [47,48].…”

Section: Cd46 In Innate Immunitysupporting

confidence: 92%

Section: Exploitation By Pathogenssupporting

confidence: 71%

“…Also, as CD46 seems to participate in the maintenance of epithelial barrier integrity [42][43][44], binding of pathogens to CD46 may facilitate direct cell entry of transgression through the protective epithelium, thereby fostering pathogen protection and dissemination [29,45,46]. This observation is in line with a recent finding that CD46 participates in the regulation of epithelial cell growth and wound healing by modulating tight junction formation [42]. Further, pathogenic E. coli take advantage of this housekeeping function of CD46 on gut epithelium and induce a dramatic decrease in transepithelial resistance in conjunction with an increase of bacterial paramigration after their binding to CD46 [42].…”

Section: Exploitation By Pathogensmentioning

confidence: 99%

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CD46 in innate and adaptive immunity: an update

Cardone¹,

Friec²,

Kemper

2011

Clinical and Experimental Immunology

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SummaryCD46 was discovered in 1986 during a search for novel C3b-binding proteins. CD46 is expressed ubiquitously and functions as a co-factor in the factor I-mediated proteolytic cleavage of C3b and C4b. Its vital role in preventing complement deposition on host tissue is underpinned by the fact that deficiency of CD46 is a predisposing factor for numerous disease conditions arising from complement-mediated 'self-attack'. However, in the last 10 years, it has become apparent that CD46 is also heavily involved in a new and somewhat surprising functional aspect of the complement system: the down-modulation of adaptive T helper type 1 (Th1) immune responses by regulating the production of interferon (IFN)-g versus interleukin (IL)-10 within these cells. Specifically, this latter function of CD46 is a tantalizing discovery -it may not only have delivered the explanation as to why so many pathogens use and abuse CD46 as cell entry receptor but clearly has important clinical implications for the better understanding of Th1-mediated disease states and novel therapeutic approaches for their amelioration. Here, we summarize and discuss the current knowledge about CD46 and its expanding roles in the immune system.

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Section: Cd46 In Innate Immunitysupporting

confidence: 92%

Section: Exploitation By Pathogenssupporting

confidence: 71%

Section: Exploitation By Pathogensmentioning

confidence: 99%

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CD46 in innate and adaptive immunity: an update

Cardone¹,

Friec²,

Kemper

2011

Clinical and Experimental Immunology

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“…These findings demonstrated that yak milk exosomes could be more capable of enhancing intestinal mucosal barrier function. Furthermore, CD46 was reported to be a key component of TJ, which directly regulated the expression of E-cadherin and TJ function to maintain epithelial cell barrier integrity (Al-Shouli et al, 2010). Here, our data provide evidence supporting that specific components of the yak milk exosomes (i.e., CD46) could potentially improve TJ function in IEC-6.…”

Section: Discussionsupporting

confidence: 72%

“…The protein CD46 is a type I transmembrane glycoprotein that links between complement and adaptive immunity, and it functions as a complement regulatory protein, protecting host cells from unwanted complement activation (Cardone et al, 2011). Protein CD46 plays an important part in the homeostasis of intestinal immunity (Sadlack et al, 1993;Kühn et al, 1993) and the maintenance of epithelial cell barrier integrity via the regulation of TJ function (Al-Shouli et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Yak milk–derived exosomes alleviate lipopolysaccharide-induced intestinal inflammation by inhibiting PI3K/AKT/C3 pathway activation

Gao

Wen

et al. 2021

Journal of Dairy Science

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Intestinal epithelial cells (IEC) are important parts of the mucosal barrier, whose function can be impaired upon various injury factors such as lipopolysaccharide. Although food-derived exosomes are preventable against intestinal barrier injuries, there have been few studies on the effect of yak milk-derived exosomes and the underlying mechanism that remains poorly understood. This study aimed to characterize the effect of exosomal proteins derived from yak and cow milk on the barrier function of IEC-6 treated with lipopolysaccharide and the relevant mechanism involved. Proteomics study revealed 392 differentially expressed proteins, with 58 higher expressed and 334 lower expressed in yak milk-derived exosomes than those in cow exosomes. Additionally, the top 20 proteins with a relatively consistent higher expression in yak milk exosomes than cow milk exosomes were identified. Protein CD46 was found to be a regulator for alleviating inflammatory injury of IEC-6. In vitro assay of the role of yak milk exosomes on survival of IEC-6 in inflammation by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay confirmed the effectiveness of yak milk exosomes to increase IEC-6 survival up to 18% for 12 h compared with cow milk exosomes (up to 12%), indicating a therapeutic effect of yak milk exosomes in the prevention of intestinal inflammation. Furthermore, yak and cow milk exosomes were shown to activate the PI3K/AKT/C3 signaling pathway, thus promoting IEC-6 survival. Our findings demonstrated an important relationship between yak and cow milk exosomes and intestinal inflammation, facilitating further understanding of the mechanisms of inflammationdriven epithelial homeostasis. Interestingly, compared with cow milk exosomes, yak milk exosomes activated the PI3K/AKT/C3 signaling pathway more to lower the incidence and severity of intestine inflammation, which might represent a potential innovative therapeutic option for intestinal inflammation.

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Lets connect: A novel role for CD46 in tight junction regulation

Cited by 2 publications

References 0 publications

CD46 in innate and adaptive immunity: an update

CD46 in innate and adaptive immunity: an update

Yak milk–derived exosomes alleviate lipopolysaccharide-induced intestinal inflammation by inhibiting PI3K/AKT/C3 pathway activation

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