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IL-15 and IFN-γ Regulation in Murine NK cells- [electronic resource]
![IL-15 and IFN-γ Regulation in Murine NK cells - [electronic resource]](/Users/Baul/Images/book.png)
IL-15 and IFN-γ Regulation in Murine NK cells- [electronic resource]
상세정보
- 자료유형
- 학위논문파일 국외
- 최종처리일시
- 20240214101653
- ISBN
- 9798380160797
- DDC
- 616.079
- 저자명
- Cimpean, Maria.
- 서명/저자
- IL-15 and IFN-γ Regulation in Murine NK cells - [electronic resource]
- 발행사항
- [S.l.]: : Washington University in St. Louis., 2023
- 발행사항
- Ann Arbor : : ProQuest Dissertations & Theses,, 2023
- 형태사항
- 1 online resource(104 p.)
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-03, Section: B.
- 주기사항
- Includes supplementary digital materials.
- 주기사항
- Advisor: Cooper, Megan A.
- 학위논문주기
- Thesis (Ph.D.)--Washington University in St. Louis, 2023.
- 사용제한주기
- This item must not be sold to any third party vendors.
- 초록/해제
- 요약Natural killer (NK) cells are innate lymphoid cells that play important roles in antiviral and antitumor responses through their cytotoxicity mechanisms and the ability to modulate immune responses through production of cytokines such as IFN-γ. NK cells are able to execute these responses rapidly and without prior sensitization due to their germline-encoded receptors. Recent work in the field of immunometabolism has highlighted the impact that changes in cellular metabolism can have on immune cell function, including NK cell effector functions. Our lab has previously reported activation-specific metabolic requirements for IFN-γ production by resting murine NK cells in vitro, which IL-15 priming, abrogates. To investigate how IL-15 priming alters the requirements for IFN-γ production, we assessed chromatin accessibility, ITAM signaling, and transcriptional changes. We found that IL-15 priming leads to a switch to transcriptional regulation of Ifng in response to activating receptor engagement, similar to cytokine-stimulated resting NK cells and in contrast to the translational regulation observed in activating receptor-stimulated resting NK cells or NK cells cultured for the same duration, in low dose IL-15. This switch in Ifng regulation in the primed cells was not due to chromatin accessibility changes in the Ifng locus or changes in ITAM signaling. Transcriptional regulation of Ifng was associated with a common signature of Myc target upregulation. To determine the potential role of Myc in IFN-γ production, two approaches were used to manipulate c-Myc: a pharmacological approach to inhibit c-Myc transcription factor activity, and a genetic model to acutely delete c-Myc. While the pharmacological approach suggested c-Myc acts as a transcription factor to regulate Ifng transcription in primed NK cells, the genetic approach revealed that c-Myc is in fact not required for Ifng transcription. In summary, this work demonstrates that IL-15 dose and culture time can dramatically alter chromatin accessibility and regulatory networks in murine NK cells, cautioning that interpretation of NK cell studies should take into account culture conditions. Furthermore, it advances our understanding of IFN-γ regulation in murine NK cells.
- 일반주제명
- Immunology.
- 일반주제명
- Cellular biology.
- 일반주제명
- Biology.
- 일반주제명
- Molecular biology.
- 키워드
- Cytokine
- 키워드
- Interferon gamma
- 키워드
- Interleukin 15
- 기타저자
- Washington University in St. Louis Biology & Biomedical Sciences (Immunology)
- 기본자료저록
- Dissertations Abstracts International. 85-03B.
- 기본자료저록
- Dissertation Abstract International
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
008240612s2023 us |||||||||||||||c||eng d■001000016934778
■00520240214101653
■006m o d
■007cr#unu||||||||
■020 ▼a9798380160797
■035 ▼a(MiAaPQ)AAI30634542
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616.079
■1001 ▼aCimpean, Maria.▼0(orcid)0000-0003-3735-2643
■24510▼aIL-15 and IFN-γ Regulation in Murine NK cells▼h[electronic resource]
■260 ▼a[S.l.]:▼bWashington University in St. Louis. ▼c2023
■260 1▼aAnn Arbor :▼bProQuest Dissertations & Theses, ▼c2023
■300 ▼a1 online resource(104 p.)
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-03, Section: B.
■500 ▼aIncludes supplementary digital materials.
■500 ▼aAdvisor: Cooper, Megan A.
■5021 ▼aThesis (Ph.D.)--Washington University in St. Louis, 2023.
■506 ▼aThis item must not be sold to any third party vendors.
■520 ▼aNatural killer (NK) cells are innate lymphoid cells that play important roles in antiviral and antitumor responses through their cytotoxicity mechanisms and the ability to modulate immune responses through production of cytokines such as IFN-γ. NK cells are able to execute these responses rapidly and without prior sensitization due to their germline-encoded receptors. Recent work in the field of immunometabolism has highlighted the impact that changes in cellular metabolism can have on immune cell function, including NK cell effector functions. Our lab has previously reported activation-specific metabolic requirements for IFN-γ production by resting murine NK cells in vitro, which IL-15 priming, abrogates. To investigate how IL-15 priming alters the requirements for IFN-γ production, we assessed chromatin accessibility, ITAM signaling, and transcriptional changes. We found that IL-15 priming leads to a switch to transcriptional regulation of Ifng in response to activating receptor engagement, similar to cytokine-stimulated resting NK cells and in contrast to the translational regulation observed in activating receptor-stimulated resting NK cells or NK cells cultured for the same duration, in low dose IL-15. This switch in Ifng regulation in the primed cells was not due to chromatin accessibility changes in the Ifng locus or changes in ITAM signaling. Transcriptional regulation of Ifng was associated with a common signature of Myc target upregulation. To determine the potential role of Myc in IFN-γ production, two approaches were used to manipulate c-Myc: a pharmacological approach to inhibit c-Myc transcription factor activity, and a genetic model to acutely delete c-Myc. While the pharmacological approach suggested c-Myc acts as a transcription factor to regulate Ifng transcription in primed NK cells, the genetic approach revealed that c-Myc is in fact not required for Ifng transcription. In summary, this work demonstrates that IL-15 dose and culture time can dramatically alter chromatin accessibility and regulatory networks in murine NK cells, cautioning that interpretation of NK cell studies should take into account culture conditions. Furthermore, it advances our understanding of IFN-γ regulation in murine NK cells.
■590 ▼aSchool code: 0252.
■650 4▼aImmunology.
■650 4▼aCellular biology.
■650 4▼aBiology.
■650 4▼aMolecular biology.
■653 ▼aCytokine
■653 ▼aInterferon gamma
■653 ▼aInterleukin 15
■653 ▼aNatural killer cells
■653 ▼aCellular metabolism
■690 ▼a0982
■690 ▼a0379
■690 ▼a0306
■690 ▼a0307
■71020▼aWashington University in St. Louis▼bBiology & Biomedical Sciences (Immunology).
■7730 ▼tDissertations Abstracts International▼g85-03B.
■773 ▼tDissertation Abstract International
■790 ▼a0252
■791 ▼aPh.D.
■792 ▼a2023
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16934778▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
■980 ▼a202402▼f2024
