The Rothenberg CURED Lab offers information about news coverage and happenings involving members of our lab, the division, division programs (Drug Allergy Program, Food Allergy Program, Transition and Adult Immunodeficiency Program) and the Cincinnati Center for Eosinophilic Disorders (CCED).
The cytokine thymic stromal lymphopoietin (TSLP) mediates type 2 immune responses, and treatments that interfere with TSLP activity are in clinical use for asthma. We investigated whether TSLP contributes to allergic inflammation by directly stimulating human CD4+ T cells and whether this process is operational in eosinophilic esophagitis (EoE), a disease linked to variants in the TSLP gene. Results from the study were published in Science Signaling. We showed relatively high levels of the TSLP receptor on esophageal-derived memory CD4+ T cells from individuals with EoE compared with control individuals. Accordingly, increased numbers of TSLP-responsive memory CD4+ T cells were present in the circulation of individuals with EoE. TSLP increased the proliferation of CD4+ T cells, enhanced type 2 cytokine production, induced the increased abundance of its own receptor, and modified the expression of 212 genes. The epigenetic response to TSLP was associated with enrichment of specific chromatin-binding sites for transcription factors (BATF and IRF4), and these transcription factors were induced by TSLP, providing a feed-forward loop. Additional data supporting a potential functional role for TSLP in driving EoE pathogenesis was reported. Taken together, these findings provide a basis for potentially developing a blood-based diagnostic test based on the extent of TSLP-induced STAT5 phosphorylation in circulating CD4+ T cells. These findings highlight the potential therapeutic value of TSLP inhibitors for treating EoE.
After one year of follow-up, a 65-center, 10-nation clinical study reinforces earlier findings that weekly dupilumab treatment for eosinophilic esophagitis produces stronger histologic, symptomatic, endoscopic, and molecular improvements compared to treatment every two weeks. Results from the study, led by Cincinnati Children’s physician–scientist Marc Rothenberg, MD, PhD, from Cincinnati Children’s, were published online Aug. 31, 2023 in The Lancet: Gastroenterology and Hepatology.
Read the Research Horizon science blog post.
Congratulations to Mario Ynga Durand, MD, PhD, research fellow in the Rothenberg CURED Lab, for receiving a 2023 Arnold W. Strauss Research Fellowship for his project "TSLP-Mediated Mechanisms of Epithelial Dysregulation in Eosinophilic Esophagitis". Read the Inspire In the Spotlight award announcement.
Marc Rothenberg has always been filled with a sense of insatiable curiosity — he even recalls turning the bathroom of his family's apartment into a lab to conduct experiments while in high school. Read more in the Lancet In Focus interview of Marc Rothenberg, MD, PhD.
The Immunology that Underlies Picky Eating
Humans can be picky eaters. One such behavior is an aversion to food associated with food allergy. The immunologic basis for this response has been uncovered in mice, revealing the role of neuroimmune connections. Read the Nature News & Views article, released online July 12, 2023, by Marc Rothenberg, MD, PhD, about the immunology underlying picky eating.
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