scholarly journals Control of Dendritic Cell Migration, T Cell-Dependent Immunity, and Autoimmunity by Protein Tyrosine Phosphatase PTPN12 Expressed in Dendritic Cells

2013 ◽  
Vol 34 (5) ◽  
pp. 888-899 ◽  
Author(s):  
Inmoo Rhee ◽  
Ming-Chao Zhong ◽  
Boris Reizis ◽  
Cheolho Cheong ◽  
André Veillette
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Genetically Engineered ◽  
Lymphoid Tissues ◽  
Peripheral Tissues ◽  
Protein Tyrosine

Dendritic cells (DCs) capture and process antigens in peripheral tissues, migrate to lymphoid tissues, and present the antigens to T cells. PTPN12, also known as PTP-PEST, is an intracellular protein tyrosine phosphatase (PTP) involved in cell-cell and cell-substratum interactions. Herein, we examined the role of PTPN12 in DCs, using a genetically engineered mouse lacking PTPN12 in DCs. Our data indicated that PTPN12 was not necessary for DC differentiation, DC maturation, or cytokine production in response to inflammatory stimuli. However, it was needed for full induction of T cell-dependent immune responsesin vivo. This function largely correlated with the need of PTPN12 for DC migration from peripheral sites to secondary lymphoid tissues. Loss of PTPN12 in DCs resulted in hyperphosphorylation of the protein tyrosine kinase Pyk2 and its substrate, the adaptor paxillin. Pharmacological inhibition of Pyk2 or downregulation of Pyk2 expression also compromised DC migration, suggesting that Pyk2 deregulation played a pivotal role in the migration defect caused by PTPN12 deficiency. Together, these findings identified PTPN12 as a key regulator in the ability of DCs to induce antigen-induced T cell responses. This is due primarily to the role of PTPN12 in DC migration from peripheral sites to secondary lymphoid organs through regulation of Pyk2.

scholarly journals The role of T‐cell protein tyrosine phosphatase in epithelial carcinogenesis

2019 ◽  
Vol 58 (9) ◽  
pp. 1640-1647
Author(s):  
Liza D. Morales ◽  
Anna K. Archbold ◽  
Serena Olivarez ◽  
Thomas J. Slaga ◽  
John DiGiovanni ◽  
...  
Keyword(s):  
T Cell ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Cell Protein ◽  
Protein Tyrosine

ROLE OF PROTEIN TYROSINE PHOSPHATASE IN MESENTERIC T CELL SUPPRESSION FOLLOWING BURN INJURY.

Shock ◽  
2001 ◽  
Vol 15 (Supplement) ◽  
pp. 13
Author(s):  
F. Haque ◽  
M. A. Choudhry ◽  
N. Fazal ◽  
R. L. Gamelli ◽  
M. M. Sayeed
Keyword(s):  
T Cell ◽  
Protein Tyrosine Phosphatase ◽  
Burn Injury ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine ◽  
T Cell Suppression ◽  
Cell Suppression

scholarly journals Macrophages Compensate for Loss of Protein Tyrosine Phosphatase N2 in Dendritic Cells to Protect from Elevated Colitis

2021 ◽  
Vol 22 (13) ◽  
pp. 6820
Author(s):  
Larissa Hering ◽  
Egle Katkeviciute ◽  
Marlene Schwarzfischer ◽  
Anna Niechcial ◽  
Julianne B. Riggs ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Lamina Propria ◽  
Protein Tyrosine Phosphatase ◽  
Immune Cell ◽  
Tyrosine Phosphatase ◽  
Cell Transfer ◽  
Protein Tyrosine ◽  
Dss Colitis ◽  
T Cell Transfer

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) plays a critical role in the pathogenesis of inflammatory bowel diseases (IBD). Mice lacking PTPN2 in dendritic cells (DCs) develop skin and liver inflammation by the age of 22 weeks due to a generalized loss of tolerance leading to uncontrolled immune responses. The effect of DC-specific PTPN2 loss on intestinal health, however, is unknown. The aim of this study was to investigate the DC-specific role of PTPN2 in the intestine during colitis development. PTPN2fl/flxCD11cCre mice were subjected to acute and chronic DSS colitis as well as T cell transfer colitis. Lamina propria immune cell populations were analyzed using flow cytometry. DC-specific PTPN2 deletion promoted infiltration of B and T lymphocytes, macrophages, and DCs into the lamina propria of unchallenged mice and elevated Th1 abundance during acute DSS colitis, suggesting an important role for PTPN2 in DCs in maintaining intestinal immune cell homeostasis. Surprisingly, those immune cell alterations did not translate into increased colitis susceptibility in acute and chronic DSS-induced colitis or T cell transfer colitis models. However, macrophage depletion by clodronate caused enhanced colitis severity in mice with a DC-specific loss of PTPN2. Loss of PTPN2 in DCs affects the composition of lamina propria lymphocytes, resulting in increased infiltration of innate and adaptive immune cells. However, this did not result in an elevated colitis phenotype, likely because increased infiltration of macrophages in the intestine upon loss of PTPN2 loss in DCs can compensate for the inflammatory effect of PTPN2-deficient DCs.

Receptor-type protein tyrosine phosphatase gamma (PTPγ), a new identifier for myeloid dendritic cells and specialized macrophages

Blood ◽  
2006 ◽  
Vol 108 (13) ◽  
pp. 4223-4231 ◽  
Author(s):  
Daniele Lissandrini ◽  
William Vermi ◽  
Marzia Vezzalini ◽  
Silvano Sozzani ◽  
Fabio Facchetti ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Protein Tyrosine Phosphatase ◽  
Human Peripheral Blood ◽  
Tyrosine Phosphatase ◽  
Advanced Pancreatic Cancer ◽  
Lymphoid Tissues ◽  
Blood Monocytes ◽  
Myeloid Dendritic Cells ◽  
Protein Tyrosine

AbstractProtein tyrosine phosphatase (PTPγ) is a receptor-like molecule with a known role in murine hematopoiesis. We analyzed the regulation of PTPγ expression in the human hematopoietic system, where it was detected in human peripheral blood monocytes and dendritic cells (DCs) of myeloid and plasmacytoid phenotypes. Its expression was maintained during in vitro monocyte differentiation to dendritic cells (moDC) and was further increased after maturation with bacterial lipopolysaccharide (LPS), CD40L, and TNFα. But PTPγ was absent when monocytes from the same donor were induced to differentiate in macrophages. B and T lymphocytes did not express PTPγ. Rather, PTPγ mRNA was expressed in primary and secondary lymphoid tissues, and the highest expression was in the spleen. PTPγ was detected by immunohistochemistry in subsets of myeloid-derived DCs and specialized macrophages (tingible bodies, sinus and alveolar macrophages). Classic macrophages in infective or reactive granulomatous reactions did not express PTPγ. Increased PTPγ expression was associated with a decreased ability to induce proliferation and interferon-γ secretion in T cells by moDCs from patients with advanced pancreatic cancer. Taken together, these results indicate that PTPγ is a finely regulated protein in DC and macrophage subsets in vitro and in vivo.

T-cell protein tyrosine phosphatase deletion results in progressive systemic inflammatory disease

Blood ◽  
2004 ◽  
Vol 103 (9) ◽  
pp. 3457-3464 ◽  
Author(s):  
Krista M. Heinonen ◽  
Frederick P. Nestel ◽  
Evan W. Newell ◽  
Gabrielle Charette ◽  
Thomas A. Seemayer ◽  
...  
Keyword(s):  
T Cell ◽  
Inflammatory Disease ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Interferon Γ ◽  
Negative Regulator ◽  
Cell Protein ◽  
Protein Tyrosine ◽  
Systemic Inflammatory Disease

Abstract The deregulation of the immune response is a critical component in inflammatory disease. Recent in vitro data show that T-cell protein tyrosine phosphatase (TC-PTP) is a negative regulator of cytokine signaling. Furthermore, tc-ptp-/- mice display immune defects and die within 5 weeks of birth. We report here that tc-ptp-/- mice develop progressive systemic inflammatory disease as shown by chronic myocarditis, gastritis, nephritis, and sialadenitis as well as elevated serum interferon-γ. The widespread mononuclear cellular infiltrates correlate with exaggerated interferon-γ, tumor necrosis factor-α, interleukin-12, and nitric oxide production in vivo. Macrophages grown from tc-ptp-/- mice are inherently hypersensitive to lipopolysaccharide, which can also be detected in vivo as an increased susceptibility to endotoxic shock. These results identify T-cell protein tyrosine phosphatase as a key modulator of inflammatory signals and macrophage function. (Blood. 2004;103:3457-3464)

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