Recruitment and functions of myeloid cells at the intersection of inflammation & remodeling / Mailyn Ann Nishiguchi.

Format:

Book

Thesis/Dissertation

Author/Creator:

Nishiguchi, Mailyn Ann, author.

Contributor:

Behrens, Edward M., degree supervisor.

University of Pennsylvania. Department of Cell and Molecular Biology, degree granting institution.

Language:

English

Subjects (All):

Genetics.

Cellular biology.

Immunology.

Cell and molecular biology--Penn dissertations.

Penn dissertations--Cell and molecular biology.

Local Subjects:

Genetics.

Cellular biology.

Immunology.

Cell and molecular biology--Penn dissertations.

Penn dissertations--Cell and molecular biology.

Genre:

Academic theses.

Physical Description:

1 online resource (129 pages)

Contained In:

Dissertations Abstracts International 82-11B.

Place of Publication:

[Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2021.

Language Note:

English

System Details:

Mode of access: World Wide Web.

text file

Summary:

Inflammation and tissue remodeling are often presented as two related, yet distinct, processes. Inflammation serves as a critical defense mechanism to destroy and clear pathogens or damaged tissue. Damaged tissue undergoes tissue remodeling, a process of reorganization that functions to maintain physiological homeostasis. Many key regulators of inflammation and tissue remodeling are shared between the two processes, yet their precise functions remain poorly understood. We sought to understand the role of pro-inflammatory circulating factors in pathological tissue remodeling using cutaneous wound healing as a model. Wounded skin remodels poorly, resulting in fibrotic scars. We observed that aging promoted tissue regeneration in the skin. In parabiosis experiments, young mice with cutaneous wounds healed with fibrosis and scar formation while aged mice healed with full-thickness tissue regeneration. Through these experiments, we identified stromal-derived factor-1 (SDF1) as a pro-fibrotic cytokine in the skin. Aging increased recruitment of enhancer of zeste homologue 2 (EZH2) and histone H3 lysine 27 trimethylation (H3K27me3) to the Sdf1 promoter. Similarly, silencing epidermal Sdf1 in young mouse skin enhanced in vivo tissue regeneration. SDF1 is a well-known mediator of macrophages. One of the key components of tissue remodeling are macrophages, which are essential for clearing apoptotic cells and remodeling the extracellular matrix. Given that crosstalk between tissues and macrophages is modulated by cytokines, we then considered the functions of a novel IL-15 responsive CD122+ macrophage population identified in the placenta, another actively remodeling tissue. In this context, we made the striking observation that CD122+ macrophages developed under the direction of interferons. Considering the canonical importance of interferons in anti-viral responses, we hypothesized that CD122+ macrophages play a critical role in promoting viral clearance. Using LCMV as a murine model of acute viral infection, we demonstrated that CD122+ macrophages modulate the abundance of CD8+ T-cells. Thus, the same macrophage phenotype found in an actively remodeling tissue also promotes an inflammatory anti-viral response. Taken together, the results presented in this dissertation highlight the role of macrophages at the intersection of tissue remodeling and anti-viral responses.

Notes:

Source: Dissertations Abstracts International, Volume: 82-11, Section: B.

Advisors: Behrens, Edward M.; Committee members: Sunny Shin; Malay Haldar; Michael Abt ; Brian Capell.

Department: Cell and Molecular Biology.

Ph.D. University of Pennsylvania 2021.

Local Notes:

School code: 0175

ISBN:

9798738617911

Access Restriction:

Restricted for use by site license.

This item is not available from ProQuest Dissertations & Theses.

This item must not be sold to any third party vendors.