Shai Bel

Bar Ilan University | BIU · Faculty of Medicine in the Galilee

The epithelial cells that line the intestine have been found to sense tight attachment of bacteria, and to respond by producing proteins that shape the effector functions of the immune system's TH17 cells.

Significance Our data demonstrate that a knockout of a single gene (tmf1) leads to the beneficial reprogramming of the gut resident microbiota. This reprogramming results in a diminished susceptibility of the genetically modified animals to induced colitis. Notably, the reprogrammed bacterial profile is transmissible, thereby conferring altered mic...

TMF/ARA160 is a Golgi-associated protein with several cellular functions, among them direction of the NF-κB subunit, p65 RelA, to ubiquitination and proteasomal degradation in stressed cells. We sought to investigate the role of TMF/ARA160 under imposed stress conditions in vivo. TMF−/− and wild-type (WT) mice were treated with the ulcerative agent...

TMF/ARA160 is a Golgi-associated protein to which several cellular activities have been attributed. These include, trafficking of Golgi-derived vesicles and E3 ubiquitin ligase activity. Here we show that TMF/ARA160 is required for the onset of key processes which underlie the development of mature sperm in mammals. TMF/ARA160 is highly expressed i...

TMF/ARA160 is a Golgi-associated protein, which is essential for spermiogenesis. In this study, we show that lack of TMF/ARA160 leads to defects in both the testis and the epididymis. In the testis, spermatid retention and extensive proliferation of Leydig cells were observed. Concomitantly, the serum levels of luteinizing hormone (LH), a stimulato...

Autophagy is a key innate immune defense mechanism in intestinal epithelial cells. Bacterial invasion of epithelial cells activates antibacterial autophagy through a process that requires the innate immune adaptor protein MYD88, yet how MYD88 signaling connects to the autophagy machinery is unknown. Here, we show that the mouse intestinal pathogen...

Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by a damaged mucus layer, which does not separate the intestinal epithelium from the microbiota. Here, we hypothesized that antibiotics affect the integrity of the mucus barrier, which allows bacterial penetrance and predisposes to intestin...

Complex lifeforms host microbiota, microbes that live synergistically with their host. Accordingly, hosts have mechanisms to defend against and tolerate the microbiota. The intestinal mucus, where these systems collide, plays a pivotal role in managing this relationship, yet lacks an integrative theoretical framework. We propose a minimal model to...

Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by a damaged mucus layer, which does not properly separate the host intestinal epithelium from the microbiota. Here, we hypothesized that antibiotics might affect the integrity of the mucus barrier. By systematically determining the effects...

Acute gastrointestinal infection with intracellular pathogens like Salmonella Typhimurium triggers the release of the proinflammatory cytokine interleukin 1β (IL-1β). However, the role of IL-1β in intestinal defense against Salmonella remains unclear. Here, we show that IL-1β production is detrimental during Salmonella infection. Mice lacking IL-1β...

Intestinal epithelial cells form the largest barrier in the body, separating us from the outside world. Here, we review recent findings that highlight the role of autophagy in the cell-intrinsic response of the epithelial cells to the harsh intestinal environment and how they shape host physiology.

Mucus secretion from colonic goblet cells is an important host defense mechanism against the harsh lumenal environment. Yet how mucus secretion is regulated is not well understood. We discovered that constitutive activation of macroautophagy/autophagy via BECN1 (beclin 1) relieves endoplasmic reticulum (ER) stress in goblet cells, which in turn pro...

Acute gastrointestinal infection with intracellular pathogens like Salmonella Typhimurium triggers the inflammasome and the release of the proinflammatory cytokine interleukin 1β (IL-1β). However, the role of IL-1β in intestinal defense against Salmonella remains unclear. Here, we show that IL-1β] production is detrimental during Salmonella infecti...

Colonic goblet cells are specialized epithelial cells that secrete mucus to physically separate the host and its microbiota, thus preventing bacterial invasion and inflammation. How goblet cells control the amount of mucus they secrete is unclear. We found that constitutive activation of autophagy in mice via Beclin 1 enables the production of a th...

Changes in microbiome composition are associated with a wide array of human diseases, turning the human microbiota into an attractive target for therapeutic intervention. Yet, clinical translation of these findings requires the establishment of causative connections between specific microbial taxa and their functional impact on host tissues. Here,...

Animals are in constant contact with the microbial world. These interactions include fending off potential pathogens and also maintaining a beneficial relationship with the microbiome. An evolutionarily conserved and widespread mechanism of achieving this balance is the production and secretion of antimicrobial peptides (AMPs). AMPs are short prote...

The mammalian intestine is colonized by trillions of microbes. To maintain a symbiotic relationship with these microbes the host creates a chemical barrier between itself and the gut microbiota. This barrier enables a mutually beneficial interaction while limiting microbial invasion into host tissues. The main components of this barrier are mucus a...

Our skin hosts bacteria, viruses, fungi, and mites, with a unique repertoire of commensal microbes at oily, moist, dry, and acral sites.¹⁻³ These organisms, collectively termed “the microbiota,” inhabit the skin surface and skin appendages, including hair follicles and sebaceous glands. The ecosystem is first established at birth, with considerable...

Metabolic plasticity is a hallmark of the ability of metastatic cancer cells to survive under stressful conditions. The intracellular Fer kinase is a selective constituent of the reprogramed mitochondria and metabolic system of cancer cells. In the current work, we deciphered the modulatory roles of Fer in the reprogrammed metabolic systems of meta...

Autoimmune diseases are complex illnesses in which the body’s immune system attacks its own healthy tissues. These diseases, which can be fatal, gravely impact the quality of life of those afflicted by them with no cure currently available. The exact etiology of autoimmune diseases is not completely clear. Biomedical research has revealed that both...

Autoimmune diseases are complex illnesses in which the body’s immune system attacks its own healthy tissues. These diseases, which can be fatal, gravely impact the quality of life of those afflicted by them with no cure currently available. The exact etiology of autoimmune diseases is not completely clear. Biomedical research has revealed that both...

Autoimmune diseases are complex illnesses in which the body’s immune system attacks its own healthy tissues. These diseases, which can be fatal, gravely impact the quality of life of those afflicted by them with no cure currently available. The exact etiology of autoimmune diseases is not completely clear. Biomedical research has revealed that both...

Vitamin A deficiency increases susceptibility to skin infection. However, the mechanisms by which vitamin A regulates skin immunity remain unclear. Here, we show that resistin-like molecule a (RELMa), a small secreted cysteine-rich protein, is expressed by epidermal keratinocytes and sebocytes and serves as an antimicrobial protein that is required...

Secretion of antimicrobial proteins is an important host defense mechanism against bacteria, yet how secretory cells maintain function during bacterial invasion has been unclear. We discovered that Paneth cells, specialized secretory cells in the small intestine, react to bacterial invasion by rerouting a critical secreted antibacterial protein thr...

Foiling bad bugs' sneaky tricks Intestinal pathogens can invade host cells and disrupt critical cellular functions, including secretion. Secretion is necessary for the delivery of antimicrobial proteins that kill pathogenic bacteria. Bel et al. show that when intestinal epithelial cells sense an invading bacterial pathogen, they “reroute” the antim...

TMF/ARA160 is known to be a TATA element Modulatory Factor (TMF). It was initially identified as a DNA-binding factor and a coactivator of the Androgen receptor. It was also characterized as a Golgi-associated protein, which is essential for acrosome formation during functional sperm development. However, the molecular roles of TMF in this intricat...

Localization of the construct 5-TMF to the Golgi apparatus depends on microtubules integrity. (A) Confocal microscope analysis of NIH3T3 cells transfected with the TMF fragment containing the MIT and c-terminus CC domain fused to EGFP (EGFP-TMF C5) (green) and immuno-stained for microtubules (red). Boxed area is enlarged and is presented in the top...

TMF co-localizes with both the cis and trans-Golgi compartments in spermatocytes. Spermatocytes were extracted from mice testes and were immuno-stained for TMF (Green), the cis-Golgi marker 58K (Red) (A), or the trans-Golgi marker Golgin97 (Red) (B). Separate channels are presented to the right of each merged image. The boxed area in each merged im...

Primers used for constructing the EGFP-TMF chimeric constructs. The numbers depict the amino acids (a.a) comprising each TMF segment. In brackets,(+) denotes the inclusion of the indicated domain, and (–) denotes the absence of the domain. CC = coiled-coil domain. MIT = microtubule interacting domain. (TIF)