Cellular and Molecular Mechanisms of Immunoregulation In Vivo
type: CreativeWork
description: Protective immunity requires a balance between pro-and anti-inflammatory responses. Absence of regulation of pro-inflammatory responses can lead to lethal tissue damage and pathologies such allergy and autoimmune disease. However, aberrant anti-inflammatory responses allow for uncontrolled pathogen replication, and progression of malignancies such as cancer. Thus, a balance between pro- and anti-inflammatory responses confers protection to the host. Redundant and non-redundant mechanisms of immunoregulation exist that establish the balance between inflammatory responses to maintain homeostasis. Also, these immunoregulatory mechanisms act at different layers of the immune response to maintain homeostasis including: epithelial barriers, innate responses, and adaptive responses. Programed death-1 (PD-1) is an inhibitory co-stimulatory molecule originally described to promote exhaustion or inhibit the function of effector T cells. PD-1 deficiency is associated with tissue specific autoimmune disease while overexpression leads to immunological anergy. In this dissertation we report a previously unknown regulatory role of PD-1 that leads to inhibition of protective immunity. PD-1 deficiency promotes the production of the immunosuppressive cytokine interleukin-10 (IL-10). Enhanced IL-10 production inhibits the production of protective type-1 cytokines that control parasite replication and render PD-1-/- mice susceptible to the protozoan parasite Toxoplasma gondii. Thus, we describe a new counter-regulatory activity of PD-1. Further, in this dissertation we report on the immunoregulatory effects of the epithelial repair protein trefoil factor 2 (TFF2). TFF2 is a well-established regulator of epithelial reconstitution. Our data demonstrates that TFF2 negatively regulates type-1 immune responses during steady state conditions. Also, following oral inoculation with T. gondii, protective immune responses are increased in TFF2-/- mice. The elevated type-1 responses correlate wit…
abstract: Protective immunity requires a balance between pro-and anti-inflammatory responses. Absence of regulation of pro-inflammatory responses can lead to lethal tissue damage and pathologies such allergy and autoimmune disease. However, aberrant anti-inflammatory responses allow for uncontrolled pathogen replication, and progression of malignancies such as cancer. Thus, a balance between pro- and anti-inflammatory responses confers protection to the host. Redundant and non-redundant mechanisms of immunoregulation exist that establish the balance between inflammatory responses to maintain homeostasis. Also, these immunoregulatory mechanisms act at different layers of the immune response to maintain homeostasis including: epithelial barriers, innate responses, and adaptive responses. Programed death-1 (PD-1) is an inhibitory co-stimulatory molecule originally described to promote exhaustion or inhibit the function of effector T cells. PD-1 deficiency is associated with tissue specific autoimmune disease while overexpression leads to immunological anergy. In this dissertation we report a previously unknown regulatory role of PD-1 that leads to inhibition of protective immunity. PD-1 deficiency promotes the production of the immunosuppressive cytokine interleukin-10 (IL-10). Enhanced IL-10 production inhibits the production of protective type-1 cytokines that control parasite replication and render PD-1-/- mice susceptible to the protozoan parasite Toxoplasma gondii. Thus, we describe a new counter-regulatory activity of PD-1. Further, in this dissertation we report on the immunoregulatory effects of the epithelial repair protein trefoil factor 2 (TFF2). TFF2 is a well-established regulator of epithelial reconstitution. Our data demonstrates that TFF2 negatively regulates type-1 immune responses during steady state conditions. Also, following oral inoculation with T. gondii, protective immune responses are increased in TFF2-/- mice. The elevated type-1 responses correlate wit…
author: McBerry, Cortez
language: English
keywords: Immunology, PD1, IL10, TFF2, Lkynurenine, lipoxin, counter regulation
date published: 2012
date modified: 2026-07-24T03:36:39Z
provider: OhioLINK
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cincinnati