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Dendritic Epidermal T Cells Seed the Perinatal Intestines and Orchestrate Early Life Immune Defenses
Dendritic Epidermal T Cells Seed the Perinatal Intestines and Orchestrate Early Life Immun...
Dendritic Epidermal T Cells Seed the Perinatal Intestines and Orchestrate Early Life Immune Defenses

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20260202105615
ISBN  
9798265429285
DDC  
570
저자명  
Gaafarelkhalifa, Mohammed Ahmed.
서명/저자  
Dendritic Epidermal T Cells Seed the Perinatal Intestines and Orchestrate Early Life Immune Defenses
발행사항  
[Sl] : Stanford University, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
162 p
주기사항  
Source: Dissertations Abstracts International, Volume: 87-05, Section: B.
주기사항  
Advisor: Butcher, Eugene.
학위논문주기  
Thesis (Ph.D.)--Stanford University, 2025.
초록/해제  
요약The intestinal epithelium forms an essential barrier between the body and external environment, yet during early life this barrier is immature and vulnerable to pathogen invasion. How immune defenses are established in the perinatal intestines prior to the development of adaptive immunity remains poorly understood. This dissertation investigates two cell types with potential contributions to early life intestinal immunity: dendritic epidermal T cells (DETCs) in the colon and the trafficking of intraepithelial lymphocyte progenitors (IELp) via somatostatin-SSTR2 signaling. In my primary work, I show that DETCs are the predominant T cell population in the perinatal colon, recruited through GPR15-GPR15L signaling. Once positioned as colonic intraepithelial lymphocytes, DETCs resemble their skin counterparts, expressing classical DETC markers, cytotoxic molecules, cytokines, and surveillance receptors. Functionally, colonic DETCs induce α-defensin expression, directly programming epithelial defenses. Loss of DETC recruitment compromises these processes and increases susceptibility to infection, underscoring their protective role in neonatal intestinal immunity.In complementary work published in Nature Immunology, I contributed to defining an SSTR2-somatostatin chemotactic axis that guides IELp homing to the intestine. SSTR2 is expressed on thymic IELp cells, while somatostatin is expressed by neuronal, immune, endothelial, and enteroendocrine cells in the neonatal colon. IELp trafficking establishes CD8αα⁺ IELs, which provide frontline protection against epithelial injury and infection. Together, these findings uncover critical pathways by which specialized T cells seed and prepare the developing intestinal epithelium and immune microenvironment for early-life immune defenses.
일반주제명  
Growth factors
일반주제명  
Infections
일반주제명  
Homeostasis
일반주제명  
Pathogens
일반주제명  
Chemokines
일반주제명  
Salmonella
일반주제명  
Cytotoxicity
일반주제명  
Wound healing
일반주제명  
Liver
일반주제명  
Mortality
일반주제명  
Colon
일반주제명  
Immune system
일반주제명  
Connective tissue
일반주제명  
Cytokines
일반주제명  
Lymphocytes
일반주제명  
Flow cytometry
일반주제명  
Inflammation
일반주제명  
Pathogenesis
일반주제명  
Adaptive immunity
일반주제명  
Small intestine
일반주제명  
Postpartum period
일반주제명  
Interferon
일반주제명  
Cellular biology
일반주제명  
Immunology
일반주제명  
Microbiology
일반주제명  
Obstetrics
일반주제명  
Pathology
일반주제명  
Pharmaceutical sciences
일반주제명  
Physiology
기타저자  
Stanford University.
기본자료저록  
Dissertations Abstracts International. 87-05B.
전자적 위치 및 접속  
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MARC

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■1001  ▼aGaafarelkhalifa,  Mohammed  Ahmed.
■24510▼aDendritic  Epidermal  T  Cells  Seed  the  Perinatal  Intestines  and  Orchestrate  Early  Life  Immune  Defenses
■260    ▼a[Sl]▼bStanford  University▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a162  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  87-05,  Section:  B.
■500    ▼aAdvisor:  Butcher,  Eugene.
■5021  ▼aThesis  (Ph.D.)--Stanford  University,  2025.
■520    ▼aThe  intestinal  epithelium  forms  an  essential  barrier  between  the  body  and  external  environment,  yet  during  early  life  this  barrier  is  immature  and  vulnerable  to  pathogen  invasion.  How  immune  defenses  are  established  in  the  perinatal  intestines  prior  to  the  development  of  adaptive  immunity  remains  poorly  understood.  This  dissertation  investigates  two  cell  types  with  potential  contributions  to  early  life  intestinal  immunity:  dendritic  epidermal  T  cells  (DETCs)  in  the  colon  and  the  trafficking  of  intraepithelial  lymphocyte  progenitors  (IELp)  via  somatostatin-SSTR2  signaling.  In  my  primary  work,  I  show  that  DETCs  are  the  predominant  T  cell  population  in  the  perinatal  colon,  recruited  through  GPR15-GPR15L  signaling.  Once  positioned  as  colonic  intraepithelial  lymphocytes,  DETCs  resemble  their  skin  counterparts,  expressing  classical  DETC  markers,  cytotoxic  molecules,  cytokines,  and  surveillance  receptors.  Functionally,  colonic  DETCs  induce  α-defensin  expression,  directly  programming  epithelial  defenses.  Loss  of  DETC  recruitment  compromises  these  processes  and  increases  susceptibility  to  infection,  underscoring  their  protective  role  in  neonatal  intestinal  immunity.In  complementary  work  published  in  Nature  Immunology,  I  contributed  to  defining  an  SSTR2-somatostatin  chemotactic  axis  that  guides  IELp  homing  to  the  intestine.  SSTR2  is  expressed  on  thymic  IELp  cells,  while  somatostatin  is  expressed  by  neuronal,  immune,  endothelial,  and  enteroendocrine  cells  in  the  neonatal  colon.  IELp  trafficking  establishes  CD8αα⁺  IELs,  which  provide  frontline  protection  against  epithelial  injury  and  infection.  Together,  these  findings  uncover  critical  pathways  by  which  specialized  T  cells  seed  and  prepare  the  developing  intestinal  epithelium  and  immune  microenvironment  for  early-life  immune  defenses.
■590    ▼aSchool  code:  0212.
■650  4▼aGrowth  factors
■650  4▼aInfections
■650  4▼aHomeostasis
■650  4▼aPathogens
■650  4▼aChemokines
■650  4▼aSalmonella
■650  4▼aCytotoxicity
■650  4▼aWound  healing
■650  4▼aLiver
■650  4▼aMortality
■650  4▼aColon
■650  4▼aImmune  system
■650  4▼aConnective  tissue
■650  4▼aCytokines
■650  4▼aLymphocytes
■650  4▼aFlow  cytometry
■650  4▼aInflammation
■650  4▼aPathogenesis
■650  4▼aAdaptive  immunity
■650  4▼aSmall  intestine
■650  4▼aPostpartum  period
■650  4▼aInterferon
■650  4▼aCellular  biology
■650  4▼aImmunology
■650  4▼aMicrobiology
■650  4▼aObstetrics
■650  4▼aPathology
■650  4▼aPharmaceutical  sciences
■650  4▼aPhysiology
■690    ▼a0379
■690    ▼a0982
■690    ▼a0410
■690    ▼a0380
■690    ▼a0571
■690    ▼a0572
■690    ▼a0719
■71020▼aStanford  University.
■7730  ▼tDissertations  Abstracts  International▼g87-05B.
■790    ▼a0212
■791    ▼aPh.D.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17360755▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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