Intrathymic innate lymphoid cells: long-lived mediators of immune regeneration (TRAN3P.905)

Innate lymphoid cells (ILC) are a newly described population of immune cells implicated in the maintenance and function of tissues as diverse as liver, gut, lung and lymph nodes. We have recently described a key role for ILC, and their production of IL-22, in endogenous thymic regeneration: a crucial process that allows for renewal of immune competence following immune depletion. Unlike other lymphoid cells, ILC were extremely radio-resistant with little depletion of cells after even lethal doses of total body irradiation. Consistent with these findings, a considerable proportion of ILC were non-cycling in steady-state conditions and expressed high levels of the anti-apoptotic protein Bcl-2. Perhaps unsurprising given their resistance to proliferation-targeted damage, a residual population of host ILC could be identified for up to 12 months after hematopoietic stem cell transplantation and these host ILC were almost exclusively non-proliferating. Intriguingly, although IL-22 appears to play a considerable role in their regenerative capacity, depletion of ILC from IL-22 deficient mice led to significantly worse recovery compared to Il22-/- mice replete with ILC. These pre-clinical studies not only help to identify the mechanisms that allow this nascent cell population to mediate its regenerative effects, but also offer a novel clinical approach to enhance T cell immunity in individuals with deficiencies due to aging, infectious disease, chemotherapy or radiation injury