CXCL13 is a constitutively expressed chemokine that controls migration of immune cells to lymphoid follicles. Previously, we found CXCL13 mRNA levels increased in rhesus macaque spleen tissues during AIDS. This led us to examine the levels and locations of CXCL13 by detailed in situ methods in cynomolgus macaque lymphoid and intestinal tissues. Our results revealed that there were distinct localization patterns of CXCL13 mRNA compared to protein in germinal centers. These patterns shifted during the course of simian immunodeficiency virus (SIV) infection, with increased mRNA expression within and around follicles during AIDS compared to uninfected or acutely infected animals. Unexpectedly, CXCL13 expression was also found in abundance in Paneth cells in crypts throughout the small intestine. Therefore, we expanded our analyses to include chemokines and antimicrobial peptides (AMPs) not previously demonstrated to be expressed by Paneth cells in intestinal tissues. We examined the expression patterns of multiple chemokines, including CCL25, as well as α-defensin 6 (DEFA6), β-defensin 2 (BDEF2), rhesus θ-defensin 1 (RTD-1), and Reg3γ in situ in intestinal tissues. Of the 10 chemokines examined, CXCL13 was unique in its expression by Paneth cells. BDEF2, RTD-1, and Reg3γ were also expressed by Paneth cells. BDEF2 and RTD-1 previously have not been shown to be expressed by Paneth cells. These findings expand our understanding of mucosal immunology, innate antimicrobial defenses, homeostatic chemokine function, and host protective mechanisms against microbial translocation.
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http://dx.doi.org/10.1128/CVI.00651-12 | DOI Listing |
Cell Mol Gastroenterol Hepatol
December 2024
Departments of Molecular & Integrative Physiology; Internal Medicine, University of Michigan, Ann Arbor, MI. Electronic address:
Intestinal stem cells replenish the epithelium throughout life by continuously generating intestinal epithelial cell types, including absorptive enterocytes, and secretory goblet, endocrine, and Paneth cells. This process is orchestrated by a symphony of niche factors required to maintain intestinal stem cells and to direct their proliferation and differentiation. Among the various mature intestinal epithelial cell types, Paneth cells are unique in their location in the stem cell zone, directly adjacent to intestinal stem cells.
View Article and Find Full Text PDFJ Transl Med
December 2024
Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
Background: Yes-associated protein 1 (YAP1) regulates the survival, proliferation, and stemness of cells, and contributes to the development of metabolic dysfunction associated fatty liver disease (MAFLD). However, the regulatory role of intestinal YAP1 in MAFLD still remains unclear.
Methods: Terminal ileal specimens were used to compare intestinal YAP1 activation in patients with and without MAFLD.
Int J Mol Sci
November 2024
Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Human milk (HM) is rich in bioactive factors promoting postnatal small intestinal development and maturation of the microbiome. HM is also protective against necrotizing enterocolitis (NEC), a devastating inflammatory condition predominantly affecting preterm infants. The HM glycosaminoglycan, hyaluronan (HA), is present at high levels in colostrum and early milk.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address:
Antibiotic abuse has led to an increasingly serious risk of antimicrobial resistance, developing alternative antimicrobials to combat this alarming issue is urgently needed. Rhesus theta defensin-1 (RTD-1) is a theta-defensin contributing to broad-spectrum bactericidal activity via the mechanisms of membrane perturbation. Intriguingly, human defensin-6 (HD6), an enteric defensin secreted by Paneth cells without direct bactericidal effect, could self-assembled into fibrous networks to trap enteric pathogens for assistance of innate immunity.
View Article and Find Full Text PDFMol Metab
December 2024
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan. Electronic address:
Objectives: Arginine vasopressin (AVP), known as an antidiuretic hormone, is also crucial in metabolic homeostasis. Although AVP receptor-deficient mice exhibit various abnormalities in glucose and lipid metabolism, the mechanism underlying these symptoms remains unclear. This study aimed to explore the involvement of the gut hormones including glucagon-like peptide-1 (GLP-1) and microbiota as essential mediators.
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