The breakdown and release of hyaluronan (HA) from the extracellular matrix has been hypothesized to act as an endogenous signal of injury. To test this hypothesis, we generated mice that conditionally overexpressed human hyaluronidase 1 (HYAL1). Mice expressing HYAL1 in skin either during early development or by inducible transient expression exhibited extensive HA degradation, yet displayed no evidence of spontaneous inflammation. Further, HYAL1 expression activated migration and promoted loss of DCs from the skin. We subsequently determined that induction of HYAL1 expression prior to topical antigen application resulted in a lack of an antigenic response due to the depletion of DCs from the skin. In contrast, induction of HYAL1 expression concurrent with antigen exposure accelerated allergic sensitization. Administration of HA tetrasaccharides, before or simultaneously with antigen application, recapitulated phenotypes observed in HYAL1-expressing animals, suggesting that the generation of small HA fragments, rather than the loss of large HA molecules, promotes DC migration and subsequent modification of allergic responses. Furthermore, mice lacking TLR4 did not exhibit HA-associated phenotypes, indicating that TLR4 mediates these responses. This study provides direct evidence that HA breakdown controls the capacity of the skin to present antigen. These events may influence DC function in injury or disease and have potential to be exploited therapeutically for modification of allergic responses.

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Thyroid hormone is a key regulator of post-embryonic vertebrate development. Skin is a biomedically important thyroid hormone target organ, but the cellular and molecular mechanisms underlying skin pathologies associated with thyroid dysfunction remain obscure. The transparent skin of zebrafish is an accessible model system for studying vertebrate skin development. During post-embryonic development of the zebrafish, scales emerge in the skin from a hexagonally patterned array of dermal papillae, like other vertebrate skin appendages such as feathers and hair follicles. We show here that thyroid hormone regulates the rate of post-embryonic dermal development through interaction with nuclear hormone receptors. This couples skin development with body growth to generate a well ordered array of correctly proportioned scales. This work extends our knowledge of thyroid hormone actions on skin by providing in-vivo evidence that thyroid hormone regulates multiple aspects of dermal development.

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INTRODUCTION: Probiotic use for management of GI conditions is becoming more popular, as it is perceived to be a natural and low-risk therapeutic option. Despite their increasing use, how patients choose to use probiotics or how GI providers make recommendations has not been well-studied. This survey aims to characterize the pattern of probiotic use by patients and GI providers. METHODS: Surveys were distributed to patients seen at a GI clinic at a single tertiary medical center. Surveys were also distributed to GI providers who attended a regional postgraduate course. Survey questions included basic demographics, indication for probiotic use, subjective clinical response to probiotics, side effects, brand of probiotics, and factors that influenced choice of probiotics. RESULTS: 76 patient surveys and 58 provider responses were collected. Patients used probiotics for general digestive health (22%), IBS (17%), and GERD (16%), while providers recommended probiotics for IBS (81%), Clostridioides difficile infection (64%), and IBD (45%). For symptoms, patients used probiotics to treat abdominal pain (38%) and bloating (26%), while providers recommended it for bloating (76%) and diarrhea (71%). 45% of patients reported improvement of GI symptoms, whereas 21% reported no improvement. Side effects were uncommon, but bloating and diarrhea were most frequently reported. Providers recommended specific brands and bacterial strains, while patients took a wide variety of brands without knowing specific strains. Most patients (82%) chose to take probiotics without their provider’s recommendations. Patients’ selection of probiotics was driven by cost, variety of strain, and number of colonies forming units. 91% of providers felt the need for more specific guidelines on probiotic use. CONCLUSION: This study shows that patients and their gastroenterologists have vastly different probiotic “prescribing” patterns. Despite a relative lack of evidence for many conditions, probiotics were frequently utilized. Patients use probiotics for different symptoms and conditions than physicians and have remarkably different factors that influence selection of a probiotic. Providers should proactively discuss current evidence on probiotic use and help patients identify key features and differences between probiotic products.