Eat more plants for influenza resilience: Antibiotic treatment worsens influenza in mice, possibly because the concomitant loss of the microbiota interrupts the production of bioactive metabolites. Steed et al. found that a microbial product, desaminotyrosine (DAT), produced by an obligate clostridial anaerobe from the digestion of plant flavonoids, is beneficial during influenza. DAT enters the bloodstream and triggers type I interferon signaling, which then augments antiviral responses by phagocytic cells. Without DAT, influenza virus causes inflammation and severe disease. Science , this issue p. 498

The intestinal epithelial tract forms a dynamic lining of the digestive system consisting of a range of epithelial cell sub-types with diverse functions fulfilling specific niches. The intestinal epithelium is more than just a physical barrier regulating nutrient uptake, rather it plays a critical role in homeostasis through its intrinsic innate immune function, pivotal regulation of antigen sensitization, and a bi-directional interplay with the microbiota that evolves with age. In this review we will discuss these functions of the epithelium in the context of food allergy.

Organoid technology has provided unique insights into human organ development, function, and diseases. Patient-derived organoids are increasingly used for drug screening, modeling rare disorders, designing regenerative therapies, and understanding disease pathogenesis. However, the use of Matrigel to grow organoids represents a major challenge in the clinical translation of organoid technology. Matrigel is a poorly defined mixture of extracellular matrix proteins and growth factors extracted from the Engelbreth–Holm–Swarm mouse tumor. The extracellular matrix is a major driver of multiple cellular processes and differs significantly between tissues as well as in healthy and disease states of the same tissue. Therefore, we envisioned that the extracellular matrix derived from a native healthy tissue would be able to support organoid growth akin to organogenesis in vivo. Here, we have developed hydrogels from decellularized human and bovine endometrium. These hydrogels supported the growth of mouse and human endometrial organoids, which was comparable to Matrigel. Organoids grown in endometrial hydrogels were proteomically more similar to the native tissue than those cultured in Matrigel. Proteomic and Raman microspectroscopy analyses showed that the method of decellularization affects the biochemical composition of hydrogels and, subsequently, their ability to support organoid growth. The amount of laminin in hydrogels correlated with the number and shape of organoids. We also demonstrated the utility of endometrial hydrogels in developing solid scaffolds for supporting high-throughput, cell culture–based applications. In summary, endometrial hydrogels overcome a major limitation of organoid technology and greatly expand the applicability of organoids to understand endometrial biology and associated pathologies.

SERPINE1/PAI-1 is elevated in the colon tissue of the most difficult-to-treat patients with IBD and leads to worsening of experimental colitis.

Rhinovirus (RV) infections in asthmatic patients are often associated with asthma exacerbation, characterized by worsened airways hyperreactivity and increased immune cell infiltration to the airways. The C-X-C chemokines, CXCL3 and CXCL5, regulate neutrophil trafficking to the lung via CXCR2, and their expression in the asthmatic lung is associated with steroid-insensitive type 2 inflammatory signatures. Currently, the role of CXCL3 and CXCL5 in regulating neutrophilic and type 2 responses in viral-induced asthma exacerbation is unknown. Inhibition of CXCL3 or CXCL5 with silencing RNAs in a mouse model of RV-induced exacerbation of asthma attenuated the accumulation of CXCR2⁺ neutrophils, eosinophils, and innate lymphoid cells in the lung and decreased production of type 2 regulatory factors IL-25, IL-33, IL-5, IL-13, CCL11, and CCL24. Suppression of inflammation was associated with decreased airways hyperreactivity, mucus hypersecretion, and collagen deposition. Similar results were obtained by employing RC-3095, which has been shown to bind to CXCR2, or by depletion of neutrophils. Our data demonstrate that CXCL3 and CXCL5 may be critical in the perpetuation of RV-induced exacerbation of asthma through the recruitment of CXCR2-positive neutrophils and by promoting type 2 inflammation. Targeting the CXCL3/CXCL5/CXCR2 axis may provide a new therapeutic approach to attenuating RV-induced exacerbations of asthma. Key Points This study explores a pathway that promotes Th2 cell inflammation in RV exacerbation. Inhibiting factors in this pathway could potentially benefit asthmatic patients.