From the ECM to the Cytoskeleton and Back: How Integrins Orchestrate T Cell Action

Epler, Jennifer; Liu, Rugao; Shimizu, Yoji

doi:10.1155/2000/86281

Cited by 14 publications

(10 citation statements)

References 131 publications

(96 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also found that the expression of active form of H-Ras induces the activation of the ␤ 1 in B cells (16). Accumulating evidence demonstrates that PI3K appears to play a central role in integrin triggering (27,32,33). One plausible explanation for such discrepant and complex nature of H-Ras functions can be considered to be that second signals induced by H-Ras may be differently involved in "on and off switch" for integrin triggering.…”

Section: Discussionmentioning

confidence: 57%

H-Ras/Mitogen-activated Protein Kinase Pathway Inhibits Integrin-mediated Adhesion and Induces Apoptosis in Osteoblasts

Tanaka¹,

Nakayamada²,

Fujimoto³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 57%

H-Ras/Mitogen-activated Protein Kinase Pathway Inhibits Integrin-mediated Adhesion and Induces Apoptosis in Osteoblasts

Tanaka¹,

Nakayamada²,

Fujimoto³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Therefore, the lack of sufficient intracellular signaling in the neonatal lymphocytes may interfere with efficient transendothelial migration. Recent studies have reported that transendothelial migration of leukocytes is regulated by integrin-mediated, calciumdependent, cytoskeletal organization (37,38). Therefore, a defect in calcium mobilization in neonatal lymphocytes may not preclude efficient adhesion to endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

TNF-α-Dependent ICAM-1- and VCAM-1-Mediated Inflammatory Responses Are Delayed in Neonatal Mice Infected with Pneumocystis carinii

Qureshi

Cook‐Mills

Doherty

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

Neonatal mice have a delayed CD4-mediated inflammatory response to Pneumocystis carinii (PC) infection in the lungs that corresponds to a delayed TNF-α response and a delayed clearance of the organisms compared with adult mice. Since TNF-α is known to drive the up-regulation of adhesion molecules, we examined the expression and function of adhesion molecules in the lungs of neonatal mice. The expression of both ICAM-1 and VCAM-1 was significantly lower in the lungs of PC-infected neonatal mice compared with adults. Additionally, migration of neonatal T cells across endothelial cells expressing VCAM-1 and monocyte chemotactic protein-1 was aberrant compared with that in adult T cells, although α4β1 integrin-mediated adhesion of neonatal lymphocytes was comparable to that of adult lymphocytes. Treatment of neonatal mice with exogenous TNF-α resulted in increased expression of ICAM-1 and VCAM-1 as well as increased expression of chemokines, resulting in infiltration of CD4+ cells into the lungs. Treatment with exogenous TNF-α resulted in a trend (although not statistically significant) toward a reduction of PC organisms from the lungs. These data indicate that neonatal lung endothelial cells do not up-regulate ICAM-1 and VCAM-1 in response to PC infection, probably due to depressed TNF-α production. Additionally, neonatal T cells are defective in the ability to migrate across endothelial cells.

show abstract

“…Integrins are one of the major families of adhesion molecules that mediate cell-ECM and cellcell interactions (2). Adhesion of T cells to ECM proteins or cellular integrin ligands is fundamental for lymphocyte development, migration, extravasation, and activation (3,4). Among the integrin family members, LFA-1 (a L /b 2 , CD11a/CD18) is essential for lymphocyte homing in lymphoid and nonlymphoid tissues, transmigration, and antigen-specific T-cell responses (3).…”

Section: Introductionmentioning

confidence: 99%

TGFβ Signaling Intersects with CD103 Integrin Signaling to Promote T-Lymphocyte Accumulation and Antitumor Activity in the Lung Tumor Microenvironment

et al. 2016

View full text Add to dashboard Cite

Homing of CD8þ T lymphocytes to the tumor microenvironment is an important step for mounting a robust antitumor immune response. TGFb is responsible for CD103 (a E b 7 ) integrin induction in activated intraepithelial CD8 þ T lymphocytes. However, the interplay between TGFb and CD103 and their contribution to T-cell infiltration and antitumor activity remain unknown. Here, we used viable human lung tumor slices and autologous tumor antigen-specific T-lymphocyte clones to provide evidence that CD103 is directly involved in T-lymphocyte recruitment within epithelial tumor islets and intratumoral early T-cell signaling. Moreover, TGFb enhanced CD103-dependent Tcell adhesion and signaling, whereas it inhibited leukocyte function-associated antigen (LFA)-1 (a L b 2 ) integrin expression and LFA-1-mediated T-lymphocyte functions. Mechanistic investigations revealed that TGFb bound to its receptors (TGFBR), which promoted the recruitment and phosphorylation of integrinlinked kinase (ILK) by TGFBR1. We further show that ILK interacted with the CD103 intracellular domain, resulting in protein kinase B (PKB)/AKT activation, thereby initiating integrin insideout signaling. Collectively, our findings suggest that the abundance of TGFb in the tumor microenvironment may in fact engage with integrin signaling pathways to promote T-lymphocyte antitumor functions, with potential implications for T-cell-based immunotherapies for cancer. Cancer Res; 76(7); 1757-69. Ó2016 AACR.

show abstract

From the ECM to the Cytoskeleton and Back: How Integrins Orchestrate T Cell Action

Cited by 14 publications

References 131 publications

H-Ras/Mitogen-activated Protein Kinase Pathway Inhibits Integrin-mediated Adhesion and Induces Apoptosis in Osteoblasts

H-Ras/Mitogen-activated Protein Kinase Pathway Inhibits Integrin-mediated Adhesion and Induces Apoptosis in Osteoblasts

TNF-α-Dependent ICAM-1- and VCAM-1-Mediated Inflammatory Responses Are Delayed in Neonatal Mice Infected with Pneumocystis carinii

TGFβ Signaling Intersects with CD103 Integrin Signaling to Promote T-Lymphocyte Accumulation and Antitumor Activity in the Lung Tumor Microenvironment

Contact Info

Product

Resources

About