Institute of Immunity and Transplantation


NF-kB signalling in T cell homeostasis

Find out about the Institute's research on NF-kB signalling in T cell homeostasis.

NF-κB is a transcription factor active in almost all cells of the body. It is required for the normal function of mature T cells. We have identified an unexpected function for NF-κB signalling during development of new T cells.

We are interested in how homeostatic signalling is transmitted in T cells. The NF-kB family of transcription factors are expressed by most cells of the body and are critical for their survival. NF-kB is essential for normal immunity, but its functions in T cells are not fully understood.

Conventionally, it is thought that NF-kB activation in T cells, typically downstream of TCR, regulates cell survival by control expression of pro-survival Bcl2 family members, and production of inflammatory cytokines.

It is also well recognised that new T cells require maturation in the periphery for many days before they can become fully functional. How this occurs and what signalling pathways are involved is completely unknown. We have now identified a novel role for NF-κB signalling in the maturation of new T cells, so called ‘recent thymic emigrants’ (RTE).

We manipulated NF-κB signalling by deleting IKK2, a key component of the IKK complex, causing a partial block in canonical NF-κB signalling.

We asked when T cells needed IKK2 signalling, by deleting it at different times in development: in the thymus, specifically after selection (1), or in fully mature peripheral T cells (2), and then assessed the homeostatic function of mature T cells.

When IKK2 was deleted after T cells had left the thymus and were fully mature (2), their survival and proliferation was normal. IKK2 is not required to transmit survival of proliferation signals to T cells.

One of the hallmark changes in RTE as they mature is their upregulation of IL-7R. IL-7R is required for normal T cell homeostasis. When IKK2 was deleted in the thymus (1), mature T cells failed to express IL-7R normally. However, deleting IKK2 in fully mature T cells did not effect IL-7R expression (2). IKK2 signalling is required to switch on IL-7R but not needed to keep on it.

NF-κB signalling is essential for normal maturation of new T cells. Our work now aims to identify the receptors required to activate NF-κB during development, and whether there are other genes regulated by this signalling.