서브메뉴
검색
Transcriptional and Functional Characterization of Spatially Separated Neutrophils in Inflamed Colonic Epithelium
Transcriptional and Functional Characterization of Spatially Separated Neutrophils in Inflamed Colonic Epithelium
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202103059
- ISBN
- 9798315797173
- DDC
- 616.07
- 서명/저자
- Transcriptional and Functional Characterization of Spatially Separated Neutrophils in Inflamed Colonic Epithelium
- 발행사항
- [Sl] : Northwestern University, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 127 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 주기사항
- Advisor: Sumagin, Ronen.
- 학위논문주기
- Thesis (Ph.D.)--Northwestern University, 2025.
- 초록/해제
- 요약Polymorphonuclear neutrophils (PMNs) are the most abundant immune cells in human circulation and serve as first responders to sites of infection or injury. While essential for frontline host defense, dysregulated PMN trafficking and activity can exacerbate inflammation and contribute to tissue damage, as seen in inflammatory bowel disease (IBD). IBD, which includes ulcerative colitis (UC) and Crohn's disease (CD), is a chronic autoimmune disorder characterized by epithelial damage and excessive PMN infiltration into the intestinal mucosa, which is associated with poor clinical outcomes. Notably, the spatial distribution of PMNs is an important clinical feature of UC, with epithelium-associated neutrophils (EANs) correlating with worse disease severity and reduced response to biologics compared to lamina propria neutrophils (LPNs). However, the extent to which EANs differ from LPNs remains largely unexplored.Furthermore, despite EANs residing in close proximity to the intestinal epithelium-and prior findings showing that circulating PMNs preferentially exit blood vessels near the crypt base proliferative zone, where intestinal stem cells reside - how EANs and newly recruited PMNs influence the epithelium, including the stem cell niche, remains unclear. This thesis aims to characterize the phenotype and function of spatially distinct LPNs and EANs, as well as investigate the impact of EANs and infiltrating neutrophils on the intestinal epithelium, including the stem cell niche.Our work demonstrates that LPNs and EANs exhibit distinct phenotypic, transcriptional, and functional signatures. Specifically, LPNs are more phagocytic and migratory and transcriptionally resemble circulating blood PMNs, whereas EANs display a terminally activated, hyperinflammatory, and ROS-producing phenotype, which is likely to have detrimental effects on the epithelium. Further investigation into the impact of PMNs on the epithelium revealed that while their presence exacerbates disease outcomes, their direct effect on the epithelium, including the stem cell niche, during active inflammation appears to be minimal, warranting further exploration.In summary, this study provides the first in-depth characterization of PMN heterogeneity within the inflamed colonic mucosa, defined by spatial localization. While definitive evidence linking EANs to epithelial damage remains elusive, our findings highlight EANs as a potential therapeutic target for enhancing mucosal healing and sustaining clinical remission in UC.
- 일반주제명
- Pathology
- 일반주제명
- Cellular biology
- 일반주제명
- Immunology
- 일반주제명
- Virology
- 기타저자
- Northwestern University Driskill Graduate Training Program in Life Sciences
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
008260126s2025 us c eng d■001000017356907
■00520260202103059
■006m o d
■007cr#unu||||||||
■020 ▼a9798315797173
■035 ▼a(MiAaPQ)AAI31933726
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616.07
■1001 ▼aYalom, Lenore Kaori.▼0(orcid)0000-0002-8693-7501
■24510▼aTranscriptional and Functional Characterization of Spatially Separated Neutrophils in Inflamed Colonic Epithelium
■260 ▼a[Sl]▼bNorthwestern University▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a127 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisor: Sumagin, Ronen.
■5021 ▼aThesis (Ph.D.)--Northwestern University, 2025.
■520 ▼aPolymorphonuclear neutrophils (PMNs) are the most abundant immune cells in human circulation and serve as first responders to sites of infection or injury. While essential for frontline host defense, dysregulated PMN trafficking and activity can exacerbate inflammation and contribute to tissue damage, as seen in inflammatory bowel disease (IBD). IBD, which includes ulcerative colitis (UC) and Crohn's disease (CD), is a chronic autoimmune disorder characterized by epithelial damage and excessive PMN infiltration into the intestinal mucosa, which is associated with poor clinical outcomes. Notably, the spatial distribution of PMNs is an important clinical feature of UC, with epithelium-associated neutrophils (EANs) correlating with worse disease severity and reduced response to biologics compared to lamina propria neutrophils (LPNs). However, the extent to which EANs differ from LPNs remains largely unexplored.Furthermore, despite EANs residing in close proximity to the intestinal epithelium-and prior findings showing that circulating PMNs preferentially exit blood vessels near the crypt base proliferative zone, where intestinal stem cells reside - how EANs and newly recruited PMNs influence the epithelium, including the stem cell niche, remains unclear. This thesis aims to characterize the phenotype and function of spatially distinct LPNs and EANs, as well as investigate the impact of EANs and infiltrating neutrophils on the intestinal epithelium, including the stem cell niche.Our work demonstrates that LPNs and EANs exhibit distinct phenotypic, transcriptional, and functional signatures. Specifically, LPNs are more phagocytic and migratory and transcriptionally resemble circulating blood PMNs, whereas EANs display a terminally activated, hyperinflammatory, and ROS-producing phenotype, which is likely to have detrimental effects on the epithelium. Further investigation into the impact of PMNs on the epithelium revealed that while their presence exacerbates disease outcomes, their direct effect on the epithelium, including the stem cell niche, during active inflammation appears to be minimal, warranting further exploration.In summary, this study provides the first in-depth characterization of PMN heterogeneity within the inflamed colonic mucosa, defined by spatial localization. While definitive evidence linking EANs to epithelial damage remains elusive, our findings highlight EANs as a potential therapeutic target for enhancing mucosal healing and sustaining clinical remission in UC.
■590 ▼aSchool code: 0163.
■650 4▼aPathology
■650 4▼aCellular biology
■650 4▼aImmunology
■650 4▼aVirology
■653 ▼aPolymorphonuclear neutrophils
■653 ▼aInflammatory bowel disease
■653 ▼aUlcerative colitis
■653 ▼aLamina propria neutrophils
■690 ▼a0571
■690 ▼a0720
■690 ▼a0379
■690 ▼a0982
■71020▼aNorthwestern University▼bDriskill Graduate Training Program in Life Sciences.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■790 ▼a0163
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17356907▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
