Elucidating the Role of Innate Immunity during Intestinal Inflammation in XIAP deficiency

Müller-Foxworth, Madeleine

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Institut für Molekulare Immunologie

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Original title:: Elucidating the Role of Innate Immunity during Intestinal Inflammation in XIAP deficiency
Translated title:: Untersuchung der Rolle des innaten Immunsystems bei entzündlichen Darmerkrankungen bei fehlender XIAP-Expression
Author:: Müller-Foxworth, Madeleine
Year:: 2024
Document type:: Dissertation
Faculty/School:: TUM School of Medicine and Health
Institution:: Institut für Molekulare Immunologie (Prof. Knolle)
Advisor:: Knolle, Percy A. (Prof. Dr.)
Referee:: Böttcher, Jan P. (Dr.); Zehn, Dietmar (Prof. Dr.)
Language:: en
Subject group:: NAT Naturwissenschaften (allgemein)
Keywords:: IBD ; monogenic ; early-onset ; XIAP ; intestinal tissue inflammation ; intraepithelial ; Lamina propria ; myeloid immune cells ; TNF ; TNFR2 ; TLR5 ; CD209a ; programmed inflammatory cell death ; DC
Translated keywords:: Darmentzündung ; monogenetisch ; pediatrisch ; XIAP ; lokale Gewebstentzündung ; intraepithelial ; Lamina propria ; myeloide Immunzellen ; TNF ; TNFR2 ; TLR5 ; CD209 ; programmmierter inflammatorischer Zelltod ; dendritische Zellen
TUM classification:: MED 450
Abstract:: Over 5 Mio. IBD patients endure lifelong relapses despite treatment. 4% of severe monogenic IBD cases are linked to XIAP deficiency. I characterized inflammation and dysbiosis in Xiap-/- mice. CD209a+ DC subsets in the ileum drive inflammation via aberrant TNF signalling through TNFR2. Xiap-/- mice show signs of dysbiosis and metabolic profile changes. This reveals XIAP's crucial role in mediating local innate immune responses. This may help refine IBD treatment by targeting mechanisms of inflammatory cell death, and microbiota-based therapies. «
Over 5 Mio. IBD patients endure lifelong relapses despite treatment. 4% of severe monogenic IBD cases are linked to XIAP deficiency. I characterized inflammation and dysbiosis in Xiap-/- mice. CD209a+ DC subsets in the ileum drive inflammation via aberrant TNF signalling through TNFR2. Xiap-/- mice show signs of dysbiosis and metabolic profile changes. This reveals XIAP's crucial role in mediating local innate immune responses. This may help refine IBD treatment by targeting mechanisms of inflam... »
Translated abstract:: Weltweit existieren über 5 Mio Fälle entzündlicher Darmerkrankungen. Etwa 4% monogener IBD-Patienten sind defizient in XIAP. Ich konnte Gewebsentzündungen des Ileums, und Dysbiose in Xiap-/- Mäusen zeigen. CD209a+ DC treiben die lokale Entzündung an. Dies erklärt die zentrale Rolle von XIAP bei entzündlichem Zelltod über den TNF-TNFR2 Signalweg. Die Ergebnisse könnten neue Therapieoptionen, etwa Anti-TNF-Behandlungen und mikrobiota-basierte Ansätze, eröffnen.
WWW:: https://mediatum.ub.tum.de/?id=1735598
Date of submission:: 05.03.2024
Oral examination:: 09.07.2024
File size:: 5020819 bytes
Pages:: 123
Urn (citeable URL):: https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20240709-1735598-1-4
Last change:: 13.02.2025
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