Discriminating the contributions of CCR4 and CCR7 to thymic central tolerance
Description: PROJECT NARRATIVE To avoid autoimmunity, maturing T cells migrate into the central region of the thymus, the medulla, where they encounter heterogeneous antigen presenting cells that display a wide variety of our own proteins, such that developing T cells that are strongly autoreactive to those proteins are either induced to undergo cell death or to become regulatory T cells that can shut down autoimmune T-cell responses. Our recent published and preliminary data suggest a novel model by which the chemokine receptors CCR4 and CCR7, which are expressed by sequential stages of developing T cells, play distinct but cooperative roles in establishing broad self-tolerance to different classes of our own proteins, namely those expressed under inflammatory conditions during infections versus those expressed at steady state in differentiated tissues, respectively. Here, we will not only test whether CCR4 and CCR7 prevent autoimmunity by inducing tolerance to distinct classes of self- antigens, expressed by different antigen presenting cells in the thymus, but we will also test whether CCR4 and CCR7 impact T-cell self-tolerance by directly regulating the ability of developing T cells to enter the medulla and undergo interactions with cells that promote tolerance therein and/or by modulating the activity and homeostasis of other cells in the thymus that educate developing T cells to become self-tolerant.
Funding type: research
Funder scheme: R01
Start date: 2014-03-15
End date: 2030-08-31
Investigator: LAUREN ILYSE RICHIE EHRLICH
Institution: UNIVERSITY OF TEXAS AT AUSTIN
Funded outputs count: 56
Funder award ID: R01AI104870
OpenAlex ID: G9000871964