Quantitative analysis reveals reciprocal regulations underlying recovery dynamics of thymocytes and thymic environment in mice

Abstract

AbstractThymic crosstalk, a set of reciprocal regulations between thymocytes and the thymic environment, is relevant for orchestrating appropriate thymocyte development as well as thymic recovery from various exogenous insults. In this work, interactions shaping thymic crosstalk and the resultant dynamics of thymocytes and thymic epithelial cells are inferred based on quantitative analysis and modeling of the recovery dynamics induced by irradiation. The analysis identifies regulatory interactions consistent with known molecular evidence and reveals their dynamic roles in the recovery process. Moreover, the analysis also predicts, and a subsequent experiment verifies, a previously unrecognized regulation of CD4+CD8+ double positive thymocytes which temporarily increases their proliferation rate upon the decrease in their population size. Our model establishes a pivotal step towards the dynamic understanding of thymic crosstalk as a regulatory network system.