The Expression Of Connexin-43 By CD11c+ Dendritic Cells Is Required to Maintain CD4+ Foxp3+ Regulatory T Cell Population in Peripheral Lymphoid Organs

<p>Foxp3⁺ regulatory T cells (T_R) are an immunosuppressive subset of CD4⁺ T cells that maintain homeostasis of the immune system. They are sustained by the interaction between the Major Histocompatibility Complex (MHC) molecules present on antigen presenting dendritic cells and the T Cell Receptor (TCR) expressed on T_R cells that is specific for the MHC loaded with an antigenic peptide. Here, we show that in addition to MHC/TCR interaction, Connexin-43 (Cx43) expression by dendritic cells is required to maintain the TR cell population. CD11c⁺ dendritic cells represent a major subset of antigen presenting cells. Using flow cytometry, we have observed that mice which lack Cx43 expression in CD11c⁺ dendritic cells (Cx43^DC-), have a lower percentage of T_R cells which express lower levels of Foxp3. These mice showed increased incidence of dermatitis as they age, even though we show that their dendritic cells can efficiently present antigen to naive T cells using proliferation inhibition assay. The decrease in the proportion of T_R cells were associated with an altered phenotype of these cells, demonstrated by lower expression of CD39 and higher expression of CD73, ectonucleotidases mediating T_R cell immunosuppressive function. We propose that the presence of Cx43 on the surface of dendritic cells is required for effective communication between T_R cells and dendritic cells so as to sustain T_R cell homeostatic expansion and Foxp3 expression.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Biological Sciences

Year dc:date.available

2019

Author dc:creator

• Miller, Caroline Titus

Contributors dc:contributor

• Piotr Kraj
• Emilia Oleszak
• Robert Ratzlaff

• Connexin
• Cx43
• Dendritic cells
• Foxp3
• Immunosuppressive
• Regulatory T cells
• Cell Biology
• Medical Immunology
• Molecular Biology

Statement dc:rights

• <p>In Copyright. URI: <a href="http://rightsstatements.org/vocab/InC/1.0/">http://rightsstatements.org/vocab/InC/1.0/</a> This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).</p>

Identifier

9781687937308

OAI identifier oai:identifier

oai:digitalcommons.odu.edu:biology_etds-1094