Differential Requirement of Kindlin-3 for T Cell Progenitor Homing to the Non-vascularized and Vascularized Thymus

Overview

Journal Elife

Specialty Biology

Date 2018 Sep 7

PMID 30187863

Citations 10

Authors

Federico Andrea Moretti

Sarah Klapproth

Raphael Ruppert

Andreas Margraf

Jasmin Weber

Robert Pick

Christoph Scheiermann

Markus Sperandio

Reinhard Fassler

Markus Moser

Affiliations

Soon will be listed here.

Abstract

The role of integrin-mediated adhesion during T cell progenitor homing to and differentiation within the thymus is ill-defined, mainly due to functional overlap. To circumvent compensation, we disrupted the hematopoietic integrin regulator kindlin-3 in mice and found a progressive thymus atrophy that is primarily caused by an impaired homing capacity of T cell progenitors to the vascularized thymus. Notably, the low shear flow conditions in the vascular system at midgestation allow kindlin-3-deficient fetal liver-derived T cell progenitors to extravasate via pharyngeal vessels and colonize the avascular thymus primordium. Once in the thymus, kindlin-3 promotes intrathymic T cell proliferation by facilitating the integrin-dependent crosstalk with thymic antigen presenting cells, while intrathymic T cell migration, maturation into single positive CD4 and CD8 T cells and release into the circulation proceed without kindlin-3. Thus, kindlin-3 is dispensable for integrin-mediated T cell progenitor adhesion and signalling at low and indispensable at high shear forces.

Citing Articles

Distinct bidirectional regulation of LFA1 and α4β7 by Rap1 and integrin adaptors in T cells under shear flow.

Kamioka Y, Ueda Y, Kondo N, Tokuhiro K, Ikeda Y, Bergmeier W Cell Rep. 2023; 42(6):112580.

PMID: 37267105 PMC: 10592472. DOI: 10.1016/j.celrep.2023.112580.

Thymic Microenvironment: Interactions Between Innate Immune Cells and Developing Thymocytes.

Wang H, Zuniga-Pflucker J Front Immunol. 2022; 13:885280.

PMID: 35464404 PMC: 9024034. DOI: 10.3389/fimmu.2022.885280.

Metabolite and thymocyte development defects in ADA-SCID mice receiving enzyme replacement therapy.

Moretti F, Giardino G, Attenborough T, Gkazi A, Margetts B, la Marca G Sci Rep. 2021; 11(1):23221.

PMID: 34853379 PMC: 8636570. DOI: 10.1038/s41598-021-02572-w.

Binding of Rap1 and Riam to Talin1 Fine-Tune β2 Integrin Activity During Leukocyte Trafficking.

Bromberger T, Klapproth S, Rohwedder I, Weber J, Pick R, Mittmann L Front Immunol. 2021; 12:702345.

PMID: 34489950 PMC: 8417109. DOI: 10.3389/fimmu.2021.702345.

Leukocyte Trafficking and Hemostasis in the Mouse Fetus : A Practical Guide.

Margraf A, Sperandio M Front Cell Dev Biol. 2021; 8:632297.

PMID: 33553174 PMC: 7858264. DOI: 10.3389/fcell.2020.632297.

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