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The Role of RNA Binding Proteins HnRNP A1 and HnRNP L in T Cells
The Role of RNA Binding Proteins HnRNP A1 and HnRNP L in T Cells
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202105632
- ISBN
- 9798270217167
- DDC
- 611.4
- 서명/저자
- The Role of RNA Binding Proteins HnRNP A1 and HnRNP L in T Cells
- 발행사항
- [Sl] : University of Pittsburgh, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 111 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-06, Section: B.
- 주기사항
- Advisor: Morel, Penelope;Kane, Lawrence P.;McGeachy, Mandy;D'Cruz, Louise;Atianand, Maninjay.
- 학위논문주기
- Thesis (Ph.D.)--University of Pittsburgh, 2024.
- 초록/해제
- 요약While RNA binding proteins (RBPs) like heterogeneous nuclear ribonucleoproteins (hnRNPs) have recently emerged as regulators of gene expression in immune cells, their effect on T-cell fate needs further investigation. HnRNPs are crucial in many aspects of RNA biogenesis, alternative splicing, expression, and function. We and others have shown that TCR signaling strength through the PI3K/Akt/mTOR pathway can control T cell differentiation. Differences in PI3K/Akt/mTOR signaling affect T cell fate and potentially Akt phosphorylation of hnRNP A1, which depends on TCR signal strength. HnRNP A1 is known to have a single Akt phosphorylation site at S199, and our lab has generated a new mutant mouse model, hnRNP A1-S199A, to study the effect that phosphorylation of the hnRNP A1-S199 has on T cell fate and function. We found that the hnRNP A1-S199A mutation did not affect the immune system at steady state compared to the wild type. We also found no difference in Th1, Th2, Th17, and Treg differentiation in vitro. Using an in vivo oral tolerance model, we saw no difference in Treg induction or Tfh differentiation and function using an NP immunization model. During T cell development, hnRNP L is known to regulate the proliferation and migration of thymic pre-T cells, as loss of hnRNP L in early T cell development results in a failure of T cells to reach the periphery. Little is known about how hnRNP L affects T cell activation and function. Our lab has used CD4Cre x Hnrnplfl/fl (KO) mice model to understand the role of hnRNP L in peripheral T cells. We found that at steady state, KO CD4+ T cell mice have normal migration from the thymus, but there is a reduction in peripheral T cell percentage and numbers. We also show that hnRNP L plays an essential role in Th1, Th2, and Tregs differentiation and T cell survival in vitro. Using two in vivo NP immunization models, we pfound hnRNP L is critical for Tfh differentiation and germinal center formation. This study shows that hnRNP A1 S199 is not a primary site of phosphorylation, and hnRNP L expression is critical for T cell function and survival.
- 일반주제명
- Thymus gland
- 일반주제명
- Cytoplasm
- 일반주제명
- Signal transduction
- 일반주제명
- Pathogens
- 일반주제명
- Cell death
- 일반주제명
- Telomerase
- 일반주제명
- Phosphatase
- 일반주제명
- Disease
- 일반주제명
- Biosynthesis
- 일반주제명
- Cytokines
- 일반주제명
- Immunology
- 일반주제명
- RNA-protein interactions
- 일반주제명
- Immune response
- 일반주제명
- Lymphocytes
- 일반주제명
- Bone marrow
- 일반주제명
- Antigens
- 일반주제명
- Phosphorylation
- 일반주제명
- Viral infections
- 일반주제명
- Apoptosis
- 일반주제명
- Cell cycle
- 일반주제명
- Transcription factors
- 일반주제명
- Cellular biology
- 일반주제명
- Virology
- 기본자료저록
- Dissertations Abstracts International. 87-06B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■006m o d
■007cr#unu||||||||
■020 ▼a9798270217167
■035 ▼a(MiAaPQ)AAI32362945
■035 ▼a(MiAaPQ)Pittsburgh46350
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a611.4
■1001 ▼aWhite, Tristan Lenora Augustus.
■24510▼aThe Role of RNA Binding Proteins HnRNP A1 and HnRNP L in T Cells
■260 ▼a[Sl]▼bUniversity of Pittsburgh▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a111 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-06, Section: B.
■500 ▼aAdvisor: Morel, Penelope;Kane, Lawrence P.;McGeachy, Mandy;D'Cruz, Louise;Atianand, Maninjay.
■5021 ▼aThesis (Ph.D.)--University of Pittsburgh, 2024.
■520 ▼aWhile RNA binding proteins (RBPs) like heterogeneous nuclear ribonucleoproteins (hnRNPs) have recently emerged as regulators of gene expression in immune cells, their effect on T-cell fate needs further investigation. HnRNPs are crucial in many aspects of RNA biogenesis, alternative splicing, expression, and function. We and others have shown that TCR signaling strength through the PI3K/Akt/mTOR pathway can control T cell differentiation. Differences in PI3K/Akt/mTOR signaling affect T cell fate and potentially Akt phosphorylation of hnRNP A1, which depends on TCR signal strength. HnRNP A1 is known to have a single Akt phosphorylation site at S199, and our lab has generated a new mutant mouse model, hnRNP A1-S199A, to study the effect that phosphorylation of the hnRNP A1-S199 has on T cell fate and function. We found that the hnRNP A1-S199A mutation did not affect the immune system at steady state compared to the wild type. We also found no difference in Th1, Th2, Th17, and Treg differentiation in vitro. Using an in vivo oral tolerance model, we saw no difference in Treg induction or Tfh differentiation and function using an NP immunization model. During T cell development, hnRNP L is known to regulate the proliferation and migration of thymic pre-T cells, as loss of hnRNP L in early T cell development results in a failure of T cells to reach the periphery. Little is known about how hnRNP L affects T cell activation and function. Our lab has used CD4Cre x Hnrnplfl/fl (KO) mice model to understand the role of hnRNP L in peripheral T cells. We found that at steady state, KO CD4+ T cell mice have normal migration from the thymus, but there is a reduction in peripheral T cell percentage and numbers. We also show that hnRNP L plays an essential role in Th1, Th2, and Tregs differentiation and T cell survival in vitro. Using two in vivo NP immunization models, we pfound hnRNP L is critical for Tfh differentiation and germinal center formation. This study shows that hnRNP A1 S199 is not a primary site of phosphorylation, and hnRNP L expression is critical for T cell function and survival.
■590 ▼aSchool code: 0178.
■650 4▼aThymus gland
■650 4▼aCytoplasm
■650 4▼aSignal transduction
■650 4▼aPathogens
■650 4▼aCell death
■650 4▼aTelomerase
■650 4▼aPhosphatase
■650 4▼aDisease
■650 4▼aBiosynthesis
■650 4▼aCytokines
■650 4▼aImmunology
■650 4▼aRNA-protein interactions
■650 4▼aImmune response
■650 4▼aLymphocytes
■650 4▼aTumor necrosis factor-TNF
■650 4▼aBone marrow
■650 4▼aAntigens
■650 4▼aPhosphorylation
■650 4▼aViral infections
■650 4▼aApoptosis
■650 4▼aCell cycle
■650 4▼aTranscription factors
■650 4▼aCellular biology
■650 4▼aVirology
■690 ▼a0982
■690 ▼a0379
■690 ▼a0720
■71020▼aUniversity of Pittsburgh.
■7730 ▼tDissertations Abstracts International▼g87-06B.
■790 ▼a0178
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17360878▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.


