Mechanisms regulating the transcription factor Hobit in CD8+ T cells

Abstract: Hobit is a transcription factor that has been shown to direct the effector differentiation of type 1 innate lymphoid cells (ILC1s) and the tissue residency fate of CD8+ T cells. Despite its importance alongside Blimp-1 in driving tissue resident memory (TRM) cell formation, the factors that can induce Hobit expression in CD8+ T cells are still unknown. In this thesis, I set out to identify such factors using a reductionist in vitro culture system and a transgenic mouse line carrying a tdTomato cassette inserted into the Hobit locus to report for the expression of Hobit. A broad range of culture conditions were tested for their ability to induce Hobit expression, including different cytokines as well as signals and conditions that aimed at mimicking the tissue-environment of TRM cells. Interestingly, I found that stimulation in the presence of IL-12 was able to induce Hobit expression in CD8+ T cells. Consistently, ex vivo analysis of effector CD8+ T cells from Lymphocytic Choriomeningitis Virus- (LCMV) and Vaccinia Virus (VV)-gp33-infected mice revealed that Hobit was expressed in terminal effector and effector memory CD8+ T cells, albeit to lower levels than in TRM cells. Blockade of IL-12 during the early antigen-presenting phase or the late effector and tissue migration phase of LCMV infection affected neither the effector CD8+ T cell responses nor TRM cell formation. In contrast, P14 T cell receptor (TCR) transgenic cells that were adoptively transferred into recipient mice followed by LCMV infection exhibited more robust effector expansion with higher percentage of CX3CR1 and KLRG1 expressing cells if cultured with IL-12 supplementation prior to the transfer. However, competitive adoptive transfer of Hobit-sufficient and Hobit-deficient P14 TCR transgenic cells into recipient mice followed by LCMV infection showed inconsistent results at the effector timepoint. Therefore, the role of Hobit in the effector responses of CD8+ T cell in vivo remains inconclusive. Taken together, this work suggests that the inflammatory cytokine IL-12 contributes to the induction of Hobit in effector CD8+ T cells. Given their shared expression pattern in effector and effector memory CD8+ T cells, human and mouse Hobit may afterall have similar functions and roles. Therefore, studying Hobit in mouse models could potentially be relevant for understanding Hobit in the human context

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Universität Freiburg, Dissertation, 2022

Klassifikation und Themen

• Schlagwort: Transkriptionsfaktor ; Genregulation

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2022
• Urheber: Saidin, Suzan
• Beteiligte Personen und Organisationen: Gasteiger, Georg ; Lämmermann, Tim ; Martin, Stefan F. ; Albert-Ludwigs-Universität Freiburg. Fakultät für Biologie ; International Max Planck Research School IMPRS

Weitere Informationen

• DOI: 10.6094/UNIFR/230431
• URN: urn:nbn:de:bsz:25-freidok-2304313
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:44 MEZ