Children’s Evaluation and Categorization of Transgender Children

Despite extant evidence of negative peer treatment of transgender adolescents and adults, little is known about how young children perceive transgender peers, particularly those who have socially transitioned or are living in line with their gender rather than sex at birth. Whereas children have been shown to be averse to gender nonconformity in peers, because many transgender children appear and behave in ways consistent with their expressed gender (but not their sex at birth), it is unclear how children evaluate these identities. In 2 studies, we investigated 5- to 10-year-old children’s (Ntotal = 113) preferences for transgender versus gender-“typical” peers who either shared their gender identity or did not. We also examined whether children categorized transgender peers by their sex or expressed gender, as it might inform their evaluations. Children preferred cisgender peers over transgender peers; however, they also liked peers of their own gender rather than the other gender (e.g., female participants preferred girls over boys), demonstrating that the oft-documented own-gender bias plays an important role even when children are reasoning about transgender peers. Children did not reliably categorize transgender peers by sex or gender; yet those who categorized transgender peers by their sex showed greater dislike of transgender peers. The current studies are the first to investigate cisgender children’s attitudes toward transgender children and suggest that perceptions of gender categorization and conformity play a role in children’s evaluations of transgender peers.</p

Butyrogenic bacteria after acute graft-versus-host disease (GVHD) are associated with the development of steroid-refractory GVHD

Key Points The presence of butyrogenic bacteria after the onset of acute GVHD associates with subsequent steroid-refractory GVHD or chronic GVHD. Butyrate inhibits human colonic stem cells from forming an intact epithelial monolayer.</jats:p

B1 Cell IgE Impedes Mast Cell-Mediated Enhancement of Parasite Expulsion through B2 IgE Blockade

Summary: Helminth infection is known for generating large amounts of poly-specific IgE. Here we demonstrate that innate-like B1 cells are responsible for this IgE production during infection with the nematode parasites Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. In vitro analysis of B1 cell immunoglobulin class switch recombination to IgE demonstrated a requirement for anti-CD40 and IL-4 that was further enhanced when IL-5 was added or when the B1 source was helminth infected mice. An IL-25-induced upregulation of IgE in B1 cells was also demonstrated. In T cell-reconstituted RAG1−/− mice, N. brasiliensis clearance was enhanced with the addition of B2 cells in an IgE-dependent manner. This enhanced clearance was impeded by reconstitution with IgE sufficient B1 cells. Mucosal mast cells mediated the B2 cell enhancement of clearance in the absence of B1 cells. The data support B1 cell IgE secretion as a regulatory response exploited by the helminth

2844. Butyrogenic Bacteria After Acute Graft vs. Host Disease Associate with the Development of Steroid Refractory GVHD

Abstract Background Steroid refractory acute graft- vs. -host-disease (GVHD) after hematopoietic cell transplantation (HCT) is highly morbid with limited treatment options. Murine studies show protection from GVHD with butyrate exposure but direct exposure of stem/progenitor cells to butyrate inhibits colonic stem cell proliferation. Methods Stool samples were collected weekly in a cohort of HCT recipients (n = 210) undergoing allogeneic transplant, and underwent 16S rRNA sequencing to determine the number and relative abundance of butyrogens. Dissociated primary human colonoid cell aggregates (200,000 per well) were plated onto collagen IV-coated transwells (0.4 µm pore size, 0.33 cm2, PET) in stem cell medium for 24 hours. From 24 hours onwards, the basal-lateral chamber was switched to differentiation medium; the apical chamber was Hanks Buffered Salt Solution (HBSS), HBSS with 10 mM butyrate sodium salt early (24 hours onwards) or late (72hours onwards). Trans-epithelial electrical resistance was measured daily. Results Retrospective chart review identified 27 recipients who developed acute GVHD of the gut, stratified to be either steroid refractory GVHD (failed to respond to 2 mg/kg of methylprednisolone) or responsive. The presence of butyrogens in the gut microbiome after the onset of severe acute GHVD of the gut associated with increased risk of steroid refractory GVHD (Figure 1; P &lt; 0.05). Direct exposure of human colonic stem/progenitor cells to butyrate inhibits the development of trans-epithelial electrical resistance; exposure after differentiation had no inhibition of barrier formation (Figure 2; P &lt; 0.05 by T-test). Conclusion Butyrogens may help prevent the development of acute GVHD of the gut, but once severe GVHD has developed may inhibit recovery due to the loss of crypt architecture exposing colonic stem cells to microbe-produced butyrate with impaired differentiation and cell replacement. Disclosures All Authors: No reported Disclosures. </jats:sec