Ptpn11 Deletion in CD4+ Cells Does Not Affect T Cell Development and Functions but Causes Cartilage Tumors in a T Cell-Independent Manner

Frontiers in Immunology
S M Shahjahan MiahLaurent Brossay

Abstract

The ubiquitously expressed tyrosine phosphatase Src homology region 2 domain-containing phosphatase-2 (SHP-2, encoded by Ptpn11) is required for constitutive cellular processes including proliferation, differentiation, and the regulation of immune responses. During development and maturation, subsets of T cells express a variety of inhibitory receptors known to associate with phosphatases, which in turn, dephosphorylate key players of activating receptor signaling pathways. We hypothesized that SHP-2 deletion would have major effects on T cell development by altering the thresholds for activation, as well as positive and negative selection. Surprisingly, using mice conditionally deficient for SHP-2 in the T cell lineage, we show that the development of these lymphocytes is globally intact. In addition, our data demonstrate that SHP-2 absence does not compromise T cell effector functions, suggesting that SHP-2 is dispensable in these cells. Unexpectedly, in aging mice, Ptpn11 gene deletion driven by CD4 Cre recombinase leads to cartilage tumors in wrist bones in a T cell-independent manner. These tumors resemble miniature cartilaginous growth plates and contain CD4-lineage positive chondrocyte-like cells. Altogether these result...Continue Reading

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Citations

Jan 15, 2020·Nature Immunology·Joanna BrzostekNicholas R J Gascoigne
Feb 24, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mayra Cruz TleugabulovaThierry Mallevaey
Nov 12, 2019·Frontiers in Immunology·Charlène NiogretGreta Guarda
Nov 16, 2018·Frontiers in Immunology·Kelly A Pike, Michel L Tremblay
Jan 12, 2021·Frontiers in Cell and Developmental Biology·Patricia Castro-SanchezRose Zamoyska

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Methods Mentioned

BETA
transgenic
Flow Cytometry
X-Ray
confocal microscopy

Software Mentioned

FCAP Array
FlowJo
Prism
GraphPad

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