Separation of graft-versus-host disease from graft-versus-leukemia responses by targeting CC-chemokine receptor 7 on donor T cells

Coghill, James M.; Carlson, Michael; Panoskaltsis‐Mortari, Angela; West, Michael O.; Burgents, Joseph E.; Blazar, Bruce R.; Serody, Jonathan S.

doi:10.1182/blood-2009-08-239848

Cited by 52 publications

(50 citation statements)

References 28 publications

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“…The adverse effects of these therapeutics often include issues of immune suppression due to the broad effects on T-cell adhesion. With this in mind it is of critical importance to better understand and leverage points of distinction between TCR and chemokine induced T-cell adhesion (3,18,19).…”

Section: Discussionmentioning

confidence: 99%

PLCε1 regulates SDF-1α–induced lymphocyte adhesion and migration to sites of inflammation

Strazza

Azoulay-Alfaguter

Peled

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Regulation of integrins is critical for lymphocyte adhesion to endothelium and migration throughout the body. Inside-out signaling to integrins is mediated by the small GTPase Ras-proximate-1 (Rap1). Using an RNA-mediated interference screen, we identified phospholipase Ce 1 (PLCe1) as a crucial regulator of stromal cell-derived factor 1 alpha (SDF-1α)-induced Rap1 activation. We have shown that SDF-1α-induced activation of Rap1 is transient in comparison with the sustained level following cross-linking of the antigen receptor. We identified that PLCe1 was necessary for SDF-1α-induced adhesion using shear stress, cell morphology alterations, and crawling on intercellular adhesion molecule 1 (ICAM-1)-expressing cells. Structurefunction experiments to separate the dual-enzymatic function of PLCe1 uncover necessary contributions of the CDC25, Pleckstrin homology, and Ras-associating domains, but not phospholipase activity, to this pathway. In the mouse model of delayed type hypersensitivity, we have shown an essential role for PLCe1 in T-cell migration to inflamed skin, but not for cytokine secretion and proliferation in regional lymph nodes. Our results reveal a signaling pathway where SDF-1α induces T-cell adhesion through activation of PLCe1, suggesting that PLCe1 is a specific potential target in treating conditions involving migration of T cells to inflamed organs.

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Section: Discussionmentioning

confidence: 99%

PLCε1 regulates SDF-1α–induced lymphocyte adhesion and migration to sites of inflammation

Strazza

Azoulay-Alfaguter

Peled

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…59 Moreover, we found that phosphorylation patterns of key downstream intermediates of CCR7 signaling (following CCL19 binding) are significantly altered (ERK1/ERK2) or delayed (MEK) in T cells isolated from Cdk5 2/2C mice ( Figure 7). …”

Section: /2cmentioning

confidence: 91%

Cyclin-dependent kinase 5 activity is required for allogeneic T-cell responses after hematopoietic cell transplantation in mice

Askew

Pareek

Eid

et al. 2017

Blood

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“…No GFP was found in mice receiving sham treatment. Detailed experimental procedures were conducted as described previously (56).…”

Section: Methodsmentioning

confidence: 99%

Type 2 innate lymphoid cells treat and prevent acute gastrointestinal graft-versus-host disease

Bruce¹,

Stefanski²,

Vincent³

et al. 2017

Journal of Clinical Investigation

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103

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Separation of graft-versus-host disease from graft-versus-leukemia responses by targeting CC-chemokine receptor 7 on donor T cells

Cited by 52 publications

References 28 publications

PLCε1 regulates SDF-1α–induced lymphocyte adhesion and migration to sites of inflammation

PLCε1 regulates SDF-1α–induced lymphocyte adhesion and migration to sites of inflammation

Cyclin-dependent kinase 5 activity is required for allogeneic T-cell responses after hematopoietic cell transplantation in mice

Type 2 innate lymphoid cells treat and prevent acute gastrointestinal graft-versus-host disease

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