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Investigating the Plasticity and Role of Peripherally Derived CD4 T Cells in the Brain at Homeostasis
Investigating the Plasticity and Role of Peripherally Derived CD4 T Cells in the Brain at Homeostasis
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202103020
- ISBN
- 9798286445653
- DDC
- 616.079
- 서명/저자
- Investigating the Plasticity and Role of Peripherally Derived CD4 T Cells in the Brain at Homeostasis
- 발행사항
- [Sl] : Yale University, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 252 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 주기사항
- Advisor: Wang, Andrew;Hafler, David A.
- 학위논문주기
- Thesis (Ph.D.)--Yale University, 2025.
- 초록/해제
- 요약Specialized immune cells residing in tissues orchestrate diverse biological functions through communication with parenchymal cells. The contribution of the innate immune compartment in the meninges and central nervous system (CNS) is well-characterized, however, whether T cells as part of the adaptive immune system reside in the brain and are involved in homeostasis is poorly understood. Here, we identify that the subfornical organ (SFO) region of the brain is a nucleus for parenchymal T cells in the steady-state brain in both mice and humans. Using unbiased transcriptomics, we found that these extravascular T cells in the mouse brain are distinct from meningeal T cells and more robustly secrete IFNγ and express tissue residence proteins, including CXCR6, which is required for their retention in the brain. These T cells are primed in the periphery by the microbiome during the weaning period and traffic from the white adipose and gastrointestinal tissues to the brain. Once established, their numbers can be modulated by either altering the gut microbiota or adipose tissue composition, such as those induced by dietary changes. In the brain, these CD4 T cell-derived IFNγ signals astrocytes to control adaptive behavior in food-deprived states. Thus, we find that CD4 T cells reside in the brain at steady state and are anatomically concentrated in the SFO in mouse and human, are transcriptionally and functionally distinct from meningeal T cells, and secrete IFNγ to maintain CNS homeostasis via a homeostatic fat-brain and gut-brain axis.
- 일반주제명
- Immunology
- 일반주제명
- Microbiology
- 일반주제명
- Neurosciences
- 일반주제명
- Molecular biology
- 키워드
- IFNγ signaling
- 기타저자
- Yale University Immunobiology
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520260202103020
■006m o d
■007cr#unu||||||||
■020 ▼a9798286445653
■035 ▼a(MiAaPQ)AAI31844414
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616.079
■1001 ▼aYoshida, Tomomi Marie.
■24510▼aInvestigating the Plasticity and Role of Peripherally Derived CD4 T Cells in the Brain at Homeostasis
■260 ▼a[Sl]▼bYale University▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a252 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisor: Wang, Andrew;Hafler, David A.
■5021 ▼aThesis (Ph.D.)--Yale University, 2025.
■520 ▼aSpecialized immune cells residing in tissues orchestrate diverse biological functions through communication with parenchymal cells. The contribution of the innate immune compartment in the meninges and central nervous system (CNS) is well-characterized, however, whether T cells as part of the adaptive immune system reside in the brain and are involved in homeostasis is poorly understood. Here, we identify that the subfornical organ (SFO) region of the brain is a nucleus for parenchymal T cells in the steady-state brain in both mice and humans. Using unbiased transcriptomics, we found that these extravascular T cells in the mouse brain are distinct from meningeal T cells and more robustly secrete IFNγ and express tissue residence proteins, including CXCR6, which is required for their retention in the brain. These T cells are primed in the periphery by the microbiome during the weaning period and traffic from the white adipose and gastrointestinal tissues to the brain. Once established, their numbers can be modulated by either altering the gut microbiota or adipose tissue composition, such as those induced by dietary changes. In the brain, these CD4 T cell-derived IFNγ signals astrocytes to control adaptive behavior in food-deprived states. Thus, we find that CD4 T cells reside in the brain at steady state and are anatomically concentrated in the SFO in mouse and human, are transcriptionally and functionally distinct from meningeal T cells, and secrete IFNγ to maintain CNS homeostasis via a homeostatic fat-brain and gut-brain axis.
■590 ▼aSchool code: 0265.
■650 4▼aImmunology
■650 4▼aMicrobiology
■650 4▼aNeurosciences
■650 4▼aMolecular biology
■653 ▼aBrain-resident CD4 T cells
■653 ▼aSubfornical organ
■653 ▼aIFNγ signaling
■690 ▼a0982
■690 ▼a0410
■690 ▼a0317
■690 ▼a0307
■71020▼aYale University▼bImmunobiology.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■790 ▼a0265
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17356705▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
