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Spleen Development and the Origin of Stromal Diversity

  • Elisa Lenti
  • Andrea Brendolan
Chapter

Abstract

The mammalian spleen is a secondary lymphoid organ that plays an important role in hematopoiesis and host defense. Consequently, asplenic or post-splenectomised patients have often increased risk of overwhelming infections as compared to normal population. Although much remains to be elucidated to fully understand the mechanisms governing spleen development, work over the past decade has provided new insights into the cellular and molecular mechanisms involved. It is now clear that spleen development requires coordination of cell fate specification, migration and differentiation, and failure to properly accomplish these stepwise processes results in spleen growth defects. Recent work has also provided new insights on the origin of mature spleen stromal cells by demonstrating the developmental relationship between the embryonic splenic mesenchyme and adult stromal microenvironment. These findings established that, with the exception of endothelial cells, all mature spleen stromal cells originate from embryonic multipotent mesenchymal precursors. Here we summarize the current knowledge on the key transcription factors involved in patterning and morphogenesis of the mouse spleen, and describe the developmental origin of spleen stromal cells.

Keywords

White Pulp Peripheral Lymphoid Tissue Lymphoid Tissue Inducer Dorsal Pancreas Lymphoid Tissue Inducer Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of Abbreviations

SMP

Splanchnic mesodermal plate

SPM

Spleno-pancreatic mesenchyme

DP

Dorsal pancreas

PBX1

Pre-B-Cell Leukemia Homeobox 1

NKX2-5

NK2 Homeobox 5

BAPX1

Bagpipe Homeobox Protein Homolog 1

SOX9

Sry-related hmg-box 9

TLX1

T-Cell Leukemia Homeobox 1

WT1

Wilms Tumor 1

SF1

Steoidogenic

NKX2-3

NK2 Homeobox 3

POD1

Podocyte-Expressed 1

RPSA

Ribosomal Protein SA

CDKN2B

Cyclin-dependent kinase 4 inhibitor B

VE-cadherin

Vascular endothelial cadherin

MAdCAM1

Mucosal vascular addressin cell adhesion molecule 1

PDGFRβ

Platelet-Derived Growth Factor Receptor, Beta

ICA

Isolated congenital asplenia

CXCL12

C-X-C motif chemokine 12, also known as stromal cell-derived factor 1 (SDF-1)

CXCL13

C-X-C motif chemokine 13, also known as B lymphocyte chemoattractant (BLC)

CCL19

C-C motif chemokine 19

CCL21

C-C motif chemokine 21

RORγt

Retinoic acid-related orphan receptor-γ t

LTβR

Lymphotoxin beta receptor

LTα1β2

Lymphotoxin-α1β2

LTi

Lymphoid tissue inducer cells

LTo

Lymphoid tissue organizer cells

LCMV

Lymphocytic choriomeningiatis virus

FRC

Fibroblastic reticular cell

FDC

Follicular dendritic cell

MRC

Marginal reticular cell

ECM

Extracellular matrix

PALS

Periasteriolar lymphoid sheet

BCR

B-cell receptor

ALO

Artificial lymphoid organs

Notes

Acknowledgements

This was supported by funding from the Italian Association for Cancer Research (Grant IG # 14511) and the Italian Ministry of Health (RF-2011-02347691) to A.B.

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Copyright information

© Springer Japan 2016

Authors and Affiliations

  1. 1.Division of Experimental OncologyIRCCS San Raffaele Scientific InstituteMilanItaly

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