Jasonia glutinosa (L.) DC., known as rock tea (RT), is traditionally used in Spain as a digestive due to its beneficial properties in bowel disorders. The pharmacological nature of these properties has not been established yet. The aim of this work was to evaluate the therapeutic utility of RT in experimental colitis and to identify chemical constituents with anti-inflammatory and/or anti-oxidative properties. RT extract was prepared with ethanol in a Soxhlet apparatus and analysed by HPLC-DAD. Superoxide radical scavenging properties, xanthine oxidase and lipoxygenase (5-LOX) inhibitory activity, and capability to lower nitric oxide (NO) and tumour necrosis factor α (TNF-α) levels were measured in cellfree and cell-based assays. In the 2.5%-dextran-sodium sulphate (DSS) injury-repair model of ulcerative colitis (UC), mice were daily treated with sulfasalazine (SSZ, as reference drug, 100 mg/kg bw), RT (5, 25 and 50 mg/kg bw, p.o.), or vehicle over 20-days. Colitis was scored daily. Colon samples were macroscopically and histopathologically examined. Protein levels of myeloperoxidase (MPO), interleukins 6, and 10 (IL-6, IL-10), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2) were studied as markers of oxidative stress and inflammatory activity. The integrity of the apical epithelial layer was assessed by immunofluorescence staining of zonula ocludens-1 (ZO-1). Finally, intestinal contractility was also evaluated by isometric myography. Fifteen phenolic compounds and three pigments were identified and quantified, of which caffeoylquinic acids, and the flavonoid, quercetin-3-O-galactoside, were the most abundant. RT extract significantly scavenged superoxide radicals, inhibited 5-LOX activity, and lowered NO and TNF-α levels. DSS-treated mice receiving RT scored clinically lower than controls during the first 3-days of DSS-treatment and during the recovery period. SSZ was less effective than RT. Anatomical and histological examination of colon samples revealed that RT significantly prevented shortening and thickening, and lowered the macroscopic damage score. RT also significantly prevented the increase of MPO activity, IL-6 levels, iNOS and COX-2 expression, the loss of ZO-1 apical expression, and normalized contractility disturbances. In conclusion, daily administration of RT showed therapeutic properties in the DSS-model of UC. The benefits of RT can likely be attributed to its anti-inflammatory and antioxidant phenolic and flavonoid constituents.

Background Innate Lymphoid Cells (ILC) develop from Common Lymphoid Precursors in the bone marrow, and ILC precursors (ILCP) migrate to mucosa where they mature, promote homeostasis, and provide a potent, antigen-non-specific sources of cytokines. Deciphering what local stimuli drive the final stages of ILCP maturation in these tissues remains a pressing question, as ILC frequencies can become dysregulated during chronic infection and inflammatory diseases. For example, Type-1 innate lymphoid cells (ILC1) are enriched in the mucosa of patients with active inflammatory bowel disease (IBD) and the impact of this accumulation remains elusive. Methods Here, we develop and use co-cultures of both murine and human iPSC-derived gut and lung organoids with ILCP and with mature ILC isolated from IBD patients’ intestinal biopsies. Results Harnessing these versatile models, we demonstrate that epithelial cells provide a complex niche capable of supporting the final maturation of all helper-like ILC1, ILC2, and ILC3. Notably, organoid identity was sufficient to robustly recapitulate tissue-specific ILC imprints and frequencies, even in the absence of microbial stimuli, other cell types, or cytokine supplementation. In addition, we show that that ILC1 drive expansion of the epithelial stem cell crypt through p38γ phosphorylation, driving a potentially pathological proliferative feedback loop between β-catenin and Cd44v6. We harnessed this model to elucidate that this phenotype was unexpectedly regulated by ILC1-derived TGFβ1. We further show that human gut ILC1 also secrete TGFβ1, and drive CD44v6 expression in both HIO epithelium and mesenchyme. As TGFβ1 is a master regulator of fibrosis, the leading indicator for surgery in IBD, we next characterised the ability of ILC1 to regulate matrix remodelling using a functionalized, synthetic hydrogel system. We show that ILC1 drive both matrix stiffening and degradation, which we posit occurs through a balance of MMP9 degradation and TGFβ1-induced fibronectin deposition. Conclusion Taken together, our work provides unprecedented insight into in situ ILC maturation, which we show to be driven by epithelial signals, and into ILC function. We also report that intestinal ILC1 modulate epithelial and matrix remodelling, which may drive either wound healing in homeostasis, but may tip toward pathology when enriched in IBD. Moreover, our work introduces a modular organoid platform, which provides exquisite control over both environmental stimuli and host genetics, making it a powerful tool for dissecting the interactions between complex mucosal tissues and rare cell subtypes in development and disease.