Research

Thymus and TEC Biology

The thymus is the only tissue capable of supporting the development of functional, yet self-tolerant T lymphocytes. The T cell “educational program” in the thymus is primarily orchestrated by thymic epithelial cells (TECs), which provide the desired microenvironment for T cell differentiation and selection (reviewed in Kadouri N, et al, Nat Rev Immunology, 2019). Therefore, one of the primary goals of the Abramson lab is to better understand the functional and molecular heterogeneity of the TEC compartment and to further elucidate the molecular mechanisms controlling TEC differentiation into different functionally-defined cell subsets.

Tolerance and Autoimmunity

One of the most remarkable characteristics of the immune system is its ability to discriminate between self and non-self antigens. This capacity is mediated by mechanisms of central and peripheral immunologic tolerance, which are essential for the maintenance of immune homeostasis and prevention of devastating autoimmunity. Therefore, in addition to dissecting the functional complexity of the thymus and of the TEC compartment, our lab is also interested in understanding how immunological tolerance to self is established in the thymus, and how breakdown of this process results in autoimmune disorders.

Cancer Immunotherapy

Our group is also interested in translating the lessons learned from our basic research in the field of central tolerance into designing novel approaches for immune-based therapies, including cancer immunotherapy. Malignant tumors represent a unique challenge to the immune system, as the immune system primarily regards them as “self-tissues” rather than alien and pathological entities that endanger the organism. Indeed, most recent data suggest that AIRE dysfunction may provide an important advantage in specifically breaking down immunological tolerance to certain tumor-associated antigens. Therefore, we also aim to harness the breakdown of immunological tolerance in AIRE-deficient individuals for cancer immunotherapy.

RORγt APCs

In addition to a TEC subpopulation in the thymus, AIRE was also reported to be expressed in rare cell population in secondary lymphoid organs. However, the identity and functional significance of these AIRE-expressing extrathymic cells (eTACs) have remained elusive. Recently, we have provided critical insights into the molecular characteristics and functional significance of this mystery eTAC population. Specifically, we found that these eTACs are a unique subset of RORyT⁺ APCs, endowed with the capacity to sense, internalize and present C. albicans, a fungus that is known to cause chronic infections in AIRE deficient patients. Indeed, eTAC-specific deletion of AIRE resulted in impaired generation of candida-specific Th17 cell clones and consequently to increased susceptibility to C. albicans infection.

Impact of steroid hormones on immunity

Steroid hormones (e.g. glucocorticoids) have long been recognized to play a critical role in regulating various aspects of the immune system, influencing both innate and adaptive immunity. In addition to glucocorticoids, other steroid hormones including sex hormones (in particular androgens) or vitamin D, were also shown to exert a profound influence on the immune system. However, the exact mechanisms detailing how androgens and vitamin D regulate the immune response and autoimmunity are incompletely understood. Therefore, our lab is also interested in deciphering the impact of androgens and of vitamin D on the immune response and development of autoimmunity.