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2016 ; 271
(1
): 56-71
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Thymus: the next (re)generation
#MMPMID27088907
Chaudhry MS
; Velardi E
; Dudakov JA
; van den Brink MR
Immunol Rev
2016[May]; 271
(1
): 56-71
PMID27088907
show ga
As the primary site of T-cell development, the thymus plays a key role in the
generation of a strong yet self-tolerant adaptive immune response, essential in
the face of the potential threat from pathogens or neoplasia. As the importance
of the role of the thymus has grown, so too has the understanding that it is
extremely sensitive to both acute and chronic injury. The thymus undergoes rapid
degeneration following a range of toxic insults, and also involutes as part of
the aging process, albeit at a faster rate than many other tissues. The thymus
is, however, capable of regenerating, restoring its function to a degree.
Potential mechanisms for this endogenous thymic regeneration include keratinocyte
growth factor (KGF) signaling, and a more recently described pathway in which
innate lymphoid cells produce interleukin-22 (IL-22) in response to loss of
double positive thymocytes and upregulation of IL-23 by dendritic cells.
Endogenous repair is unable to fully restore the thymus, particularly in the aged
population, and this paves the way toward the need for exogenous strategies to
help regenerate or even replace thymic function. Therapies currently in clinical
trials include KGF, use of the cytokines IL-7 and IL-22, and hormonal modulation
including growth hormone administration and sex steroid inhibition. Further novel
strategies are emerging in the preclinical setting, including the use of
precursor T cells and thymus bioengineering. The use of such strategies offers
hope that for many patients, the next regeneration of their thymus is a step
closer.
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