The contribution of TSLP to Trichuris immunity

Abstract

Recent developments in the field of alarmin immunology have altered the paradigm of their basic role, from epithelium derived influencers of dendritic cell activation state and shapers of early immunity to multi-sourced enablers of effective lymphocyte function in tissues. Literature investigating the role of thymic stromal lymphopoietin in contributing to expulsion of the intestinal parasite Trichuris muris contains important gaps which leaves much to be characterised regarding the mechanisms of contribution. Work in this thesis finds no role for caecal epithelial cells in producing TSLP at homeostasis or in response to Trichuris, instead observing upregulation of the alarmin in the lamina propria during the second and third weeks of infection. Contributions by telocytes and CCL24+ cells, two producers of TSLP recently characterised in other tissues and challenges, are likewise ruled out. Single cell sequencing and Hyperion imaging mass cytometry is used to examine the infected caecum, observing unusual Tr1-like markers on TH2 cells, transcriptional data indicating a possible CCL1/CCL8-CCR8 mechanism of TH2 cell recruitment to the infected caecum. This suggests that TH2 cells may represent the major recipient of TSLP signals, rather than dendritic cells, with timed neutralisation of TSLP suggesting maximum impact on parasite expulsion between days 15 and 30 post- infection. A role for IL-33 in shaping immunity is not observed, but induction of cytoplasmic expression in the caecal lamina propria, with no epithelial expression, is noted. With no Il25 detected in the caecum, alarmins in this tissue and model appear, according to this data, entirely non-epithelial in origin.

Date of Award	24 Jun 2025
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Richard Grencis (Main Supervisor) & Kevin Couper (Co Supervisor)