SUMMARY RORγt+ Th17 cells are important for mucosal defenses, but also contribute to autoimmune disease. They accumulate in the intestine in response to microbiota and produce IL-17 cytokines. Segmented filamentous bacteria (SFB) are Th17-inducing commensals that potentiate autoimmunity in mice. RORγt+ T cells were induced in mesenteric lymph nodes early after SFB colonization and distributed across different segments of the gastrointestinal tract. However, robust IL-17A production was restricted to the ileum, where SFB makes direct contact with the epithelium and induces serum amyloid A proteins 1 and 2 (SAA1/2), which promote local IL-17A expression in RORγt+ T cells. We identified an SFB-dependent role of type 3 innate lymphoid cells (ILC3), which secreted IL-22 that induced epithelial SAA production in a Stat3-dependent manner. This highlights the critical role of tissue microenvironment in activating effector functions of committed Th17 cells, which may have important implications for how these cells contribute to inflammatory disease.

No abstract

Th17 lymphocytes protect mucosal barriers from infections, but also contribute to multiple chronic inflammatory diseases. Their differentiation is controlled by RORγt, a ligand-regulated nuclear receptor. We identified the DEAD-box RNA helicase DDX5 as a RORγt partner that coordinates transcription of selective Th17 genes and is required for Th17-mediated inflammatory pathologies. Surprisingly, the ability of DDX5 to interact with RORγt and co-activate its targets depends on its intrinsic RNA helicase activity and binding of a conserved nuclear long noncoding RNA (lncRNA), Rmrp, which is mutated in Cartilage-Hair Hypoplasia (CHH) patients. A targeted Rmrp mutation in mice, corresponding to one in CHH patients, abrogated the lncRNA’s chromatin recruitment, ability to potentiate DDX5-RORγt interaction and RORγt target gene transcription. Elucidation of the link between Rmrp and the DDX5-RORγt complex reveals a role for RNA helicases and lncRNAs in tissue-specific transcriptional regulation and promises new opportunities for therapeutic intervention in Th17-dependent diseases.

Introduction: While great strides have been made in favor of the LGBT community overall, transgender individuals are still facing many legal challenges and suffer from more marked health issues and disparities compared to other members of the LGBT community. Our multimodal transgender curriculum was designed in accordance with the Kern model to address educational gaps in the area of transgender health. Methods: This three-part module consists of: (1) a didactic PowerPoint presentation reviewing unique health issues and disparities experienced by transgender patients, (2) a small-group session viewing and analyzing a pair of videos showcasing competent and poor communication between a provider and a transgender patient, and (3) a large-group patient panel featuring members of the transgender community. Results: One hundred and sixty-one students returned pre-and postworkshop surveys with 123 matched pairs. When comparing participants reported pre-and postworkshop confidence levels, the mean rating increased significantly for all three learning objectives. Based on a 5-point Likert scale (1 = poor, 5 = excellent), participants' mean ratings were highest for the patient panel at 4.5, compared to 3.9 for the large-group didactic lecture, and 3.8 for the small-group video session. Discussion: The use of this multimodal approach using a didactic session, video-based case discussion, and patient panel provided a strong foundation and primer for transgender health and resulted in an increase in learner confidence in module objectives regarding care for the transgender community.

No abstract