The thymus is a primary lymphoid organ that establishes and maintains the stromal microenvironments required for the development of self-tolerant, functional T cells. This microenvironment is comprised primarily of TECs and is essential for T cell development, differentiation, and proliferation. Identifying, functionally characterizing, and mapping TEC patterning throughout the developmental program is vital to understanding thymus organogenesis (development), homeostasis (maintenance), and involution (age related diminished activity). An alteration in immune response can arise from a variety of medical conditions ranging from inflammation to autoimmunity to immune deficiency to leukemia. Once a person has entered into early adulthood the thymus is already undergoing a reduction in thymus size and function termed age-associated involution, the functional impacts of this decline are not significant until late middle age in humans. Therefore, characterizing TEC pattern shifts in the involuting thymus and investigating how TEC motifs diverge from the homeostatic program is paramount to understanding not only the structure of the peripheral T cell pool and its ability to generate an immune response, but also how it breaks down in disease or aging. Thymus heterogeneity has undoubtedly complicated investigations of the molecular and cellular events underlying the organ’s development, homeostasis, and involution. Thus, there is a critical need for a comprehensive examination into the localization and covariance of the cellular components of the microenvironment on an organ-wide scale. This body of work was designed to fill this unmet need by investigating the three-dimensional architecture of the thymus and generating multidimensional maps of microscale interactions in the context of macroscale anatomical structures and networks offering insights in to the aging thymus and its corresponding diminished immune response.
