Rat Stem‐Cell Factor Induces Splenocytes Capable Of Regenerating The Thymus

Medlock, Eugene S.; Migita, Russell; Trebasky, Lisa D.; Housman, Jerry; Elliott, Gary; Hendren, R. Wayne; Deprince, Randolph B.; Greiner, Dale L.

doi:10.1155/1992/78751

Cited by 6 publications

(2 citation statements)

References 40 publications

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“…While FLT3L administration expanded peripheral DCs and pTreg numbers, this was not accompanied by increases in thymic Treg ( 36 ). Furthermore, G-CSF had no impact on thymocyte progenitor activity in rats ( 37 ). Our data therefore implicate G-CSF in the expansion of mTEC progenitors, but only when associated with FLT3L-mediated DC expansion, and suggest the hypothesis that expansion of the appropriate DC subset in the thymus can signal proliferation of mTECs from progenitors ( 38 ), providing a niche for tTreg development.…”

Section: Discussionmentioning

confidence: 98%

Autoimmune-Mediated Thymic Atrophy Is Accelerated but Reversible in RelB-Deficient Mice

et al. 2018

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Polymorphisms impacting thymic function may decrease peripheral tolerance and hasten autoimmune disease. The NF-κB transcription factor subunit, RelB, is essential for the development and differentiation of medullary thymic epithelial cells (mTECs): RelB-deficient mice have reduced thymic cellularity and markedly fewer mTECs, lacking AIRE. The precise mechanism of this mTEC reduction in the absence of RelB is unclear. To address this, we studied mTECs and dendritic cells (DCs), which critically regulate negative selection, and thymic regulatory T-cells (tTreg) in RelB−/− mice, which have spontaneous multiorgan autoimmune disease. RelB−/− thymi were organized, with medullary structures containing AIRE− mTECs, DCs, and CD4+ thymocytes, but fewer tTreg. Granulocytes infiltrated the RelB−/− thymic cortex, capsule, and medulla, producing inflammatory thymic medullary atrophy, which could be treated by granulocyte depletion or RelB+ DC immunotherapy, with concomitant recovery of mTEC and tTreg numbers. These data indicate that central tolerance defects may be accelerated by autoimmune thymic inflammation where impaired RelB signaling impairs the medullary niche, and may be reversible by therapies enhancing peripheral Treg or suppressing inflammation.

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Section: Discussionmentioning

confidence: 98%

Autoimmune-Mediated Thymic Atrophy Is Accelerated but Reversible in RelB-Deficient Mice

et al. 2018

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“…Our future studies will focus on determining the efficacy of therapeutic interventions such as growth factors and/or cells administration in combination with lymph node transplants to boost thymic epithelial cell proliferation, which may mediate downstream effects of thymus function [36][37][38]. In addition, it would be interesting to determine whether transplanting a newborn thymus in the lymph node of an aging mouse would rejuvenate immune function in these mice.…”

Section: Discussionmentioning

confidence: 99%

Thymic Rejuvenation by Adult Grafts in the Lymph Node

Rao

Gupta²,

Lagasse

2022

Preprint

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Immunologic aging is defined as a process in which the immune system undergoes tremendous decline in T cell numbers and function, thus affecting one’s ability to effectively mount an immune response. The degeneration of the thymus, the primary immune organ responsible for T cell development, is central to immunologic aging. Various studies have assessed thymic regeneration as an effective way to offset immune function decline. In this study, we determined the effect of mouse adult thymus transplants in the lymph node of athymic nude mice to rejuvenate thymus function. We transplanted thymuses of increasing ages and assessed engrafted ectopic thymuses by histology as well as for blood T cell numbers and function. We observed that transplanting aged thymuses, up to 8 months old, in the lymph node regenerated thymus function and corresponding T cell activation with some thymic rejuvenation when compared to the expected native thymus in control animals. However, transplanting 11- and 14-month old thymus in the lymph node had decreased-to-limited thymic function with no thymic rejuvenation detected. These observations provide important insights into the plasticity and regenerative capabilities of the thymus during age-associated involution.

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