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The Proteostasis of Thymic Stromal Cells in Health and Diseases

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Abstract

The thymus is the key immune organ for the development of T cells. Different populations of thymic stromal cells interact with T cells, thereby controlling the dynamic development of T cells through their differentiation and function. Proteostasis represents a balance between protein expression, folding, and modification and protein clearance, and its fluctuation usually depends at least partially on related protein regulatory systems for further survival and effects. However, in terms of the substantial requirement for self-antigens and their processing burden, increasing evidence highlights that protein regulation contributes to the physiological effects of thymic stromal cells. Impaired proteostasis may expedite the progression of thymic involution and dysfunction, accompanied by the development of autoimmune diseases or thymoma. Hence, in this review, we summarize the regulation of proteostasis within different types of thymic stromal cells under physiological and pathological conditions to identify potential targets for thymic regeneration and immunotherapy.

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No datasets were generated or analysed during the current study.

Abbreviations

TSC:

Thymic stromal cell

TEC:

Thymic epithelial cell

ERQC:

Endoplasmic reticulum quality control system

ERAD:

Endoplasmic reticulum-associated degradation

UPS:

Ubiquitin-proteasome system

UPR:

Unfolding protein response

CMJ:

Cortical-medullary junction

cTEC:

Cortical thymic epithelial cell

mTEC:

Medullary epithelial cell

TRAs:

Tissue restricted antigens

ECM:

Extracellular matrix

Fb:

Fibroblast

CapFb:

Capsular fibroblast

mFb:

Medullary fibroblast

MSC:

Mesenchymal stem cells

MEx:

Mesenchymal stromal cell-derived extracellular vesicle

tDC:

Thymic dendritic cells

SIRPα:

Signal-regulated proteinα

PV:

Perivascular space

HSC:

Hematopoietic progenitor cell

BM:

Blood-thymus barrier

ECMs:

Extracellular matrix components

TPEC:

Thymic portal endothelial cell

EMT:

Epithelial-mesenchymal transition

ETPs:

Early T lineage progenitor

TNFRSF:

Tumor necrosis factor receptor super family

LTβR:

Lymphotoxin β receptor

NF-κB:

Nuclear factor kappa-B

tTreg:

Thymic regulatory T cell

OPG:

Osteoprotegerin

Fezf2:

Forebrain embryonic zinc fingerlike protein 2

pGE:

Promiscuous gene expression

chd4:

Chromodomain helicase DNA binding protein 4

Aire:

Autoimmune regulator

Fn1:

Fibronectin 1

FGF:

Fibroblast growth factor

TGF-β1:

Transforming growth factor β1

VEGF:

Vascular endothelial growth factor

VEC:

Vascular endothelial cell

iTPEC:

Immigration TPEC

eTPEC:

Egress TPEC

S1P:

Sphingosine 1-phosphate

CP:

Core particle

RP:

Regulatory particle

chd5:

Chromodomain helicase DNA binding protein 5

MMP9:

Metalloproteinase 9

RIDD:

IRE1α-dependent decay

LAMP2:

Lysosomal-associated membrane protein 2

TSSP:

Thymus-Specific Serine Peptidase

TRAF6:

TNF receptor associated factor 6

EAE:

Experimental autoimmune encephalomyelitis

IFNλ:

Interferonλ

PPARγ:

Peroxisome proliferator-activated receptorγ

TETs:

Thymic epithelial tumors

TME:

Tumor microenvironment

cFLIP:

Cellular FLICE-like Inhibitory Protein

TRECs:

T cell receptor excision circles

RTEs:

Recent thymic emigrants

MG:

Myasthenia Gravis

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Acknowledgements

These studies were supported by 81871234, 82172763 from the National Natural Science Foundation, China.

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  1. Department of Immunology, School of Medicine, Jiangsu University, 301, Xuefu Road, Zhenjiang, Jiangsu, 212013, China

    Ting Liu & Sheng Xia

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Liu, T., Xia, S. The Proteostasis of Thymic Stromal Cells in Health and Diseases. Protein J (2024). https://doi.org/10.1007/s10930-024-10197-x

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