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Thymus

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Immunopathology in Toxicology and Drug Development

Part of the book series: Molecular and Integrative Toxicology ((MOLECUL))

Abstract

The thymus is a primary lymphoid organ where developing T cells (thymocytes) proliferate and differentiate before entering the systemic circulation to populate secondary lymphoid tissues and form the functional T cell repertoire. The thymus tightly controls the antigen specificity of these naive T cells in order to limit reaction with self antigens. In keeping with the importance of T cells to the health of the animal, their development and function are subject to many overlapping pathways and checkpoints. Therefore, many of the key players involved in T lymphocyte development, differentiation and function are potential targets for pharmaceutical intervention in aberrant T cell immune responses resulting in disease. This chapter outlines the complex function of the thymus, the range of changes seen as part of normal physiological and disease processes, and its response to immunotoxicants.

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Abbreviations

AIDz:

Autoimmune disease

AIRE:

Autoimmune regulator gene

APCs:

Antigen-presenting cells

APS:

Autoimmune polyendocrinopathy syndrome

CTL:

Cytotoxic T cells (CD8+)

CTLA-4:

Cytotoxic T lymphocyte antigen

DOCK8:

Dedicator of cytokinesis 8 protein

ETPs:

Early thymic progenitor cells

FOXP3:

Transcription factor forkhead box P3

iTreg:

Induced regulatory T-cells

Lck:

Lymphocyte-specific protein tyrosine kinase

MHC:

Major histocompatibility complex

nTreg:

Natural regulatory T cells (CD4+ CD25+ FOXP3+)

PD-1:

Programmed death-1

PSGL1:

P-selectin glycoprotein ligand 1

Rag1 and Rag2:

Recombinase-activating genes 1 and 2

Runx3:

Runt related transcription factor 3

S1P:

Sphingosine 1-phosphate

S1P1/S1PR1:

S1P receptor 1

Syk:

Spleen tyrosine kinase

T-bet:

T-box transcription factor

TCR:

T cell receptor (CD3)

TEC:

Thymic epithelial cells

Th:

T helper cells (CD4+)

Th0:

Naıve T-cells

ThPOK:

Th-inducing BTB/POZ domain-containing Kruppel-like zinc-finger transcription factor

TREG/Treg:

Regulatory T cell

ZAP-70:

Zeta chain associated protein-70

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  1. GSK, Ware, Hertfordshire, SG120DP, UK

    Gail Pearse B.V.M. & S., D.A.C.V.P.

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    George A. Parker

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Pearse, G. (2017). Thymus. In: Parker, G. (eds) Immunopathology in Toxicology and Drug Development. Molecular and Integrative Toxicology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-47385-7_1

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