TŻ

Tomasz Żal

The University of Texas MD Anderson Cancer Center

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Wei Cao

The University of Texas Health Science Center at Houston

Michel Gilliet

University of Lausanne

Jae–Hoon Chang

Yeungnam University

Shao‐Cong Sun

Northwestern Polytechnical University

Mikyoung Chang

The University of Texas MD Anderson Cancer Center

Yichuan Xiao

Shanghai Institute of Nutrition and Health

Malgorzata Anna Zal

The University of Texas MD Anderson Cancer Center

Jacco van Rheenen

The Netherlands Cancer Institute

Jens‐Michael Schröder

University Hospital Schleswig-Holstein

David M. Guimond

Gossamer Bio (United States)

Cooperative Institutions

The University of Texas MD Anderson Cancer Center

Oncode Institute

The University of Texas Health Science Center at Houston

The Netherlands Cancer Institute

Scripps Research Institute

University of Houston

San Diego State University

University of Lausanne

La Jolla Institute for Immunology

The University of Texas at Austin

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Tissue-resident memory CD8 ⁺ T cells continuously patrol skin epithelia to quickly recognize local antigen

Proceedings of the National Academy of Sciences (2012)

Silvia Ariotti Joost B. Beltman Grzegorz Chodaczek Mirjam E. Hoekstra Anna E. van Beek

Recent work has demonstrated that following the clearance of infection a stable population of memory T cells remains present in peripheral organs and contributes to the control of secondary infections. However, little is known about how tissue-resident memory T cells behave in situ and how they encounter newly infected target cells. Here we demonstrate that antigen-specific CD8 + T cells that remain in skin following herpes simplex virus infection show a steady-state crawling behavior in between keratinocytes. Spatially explicit simulations of the migration of these tissue-resident memory T cells indicate that the migratory dendritic behavior of these cells allows the detection of antigen-expressing target cells in physiologically relevant time frames of minutes to hours. Furthermore, we provide direct evidence for the identification of rare antigen-expressing epithelial cells by skin-patrolling memory T cells in vivo. These data demonstrate the existence of skin patrol by memory T cells and reveal the value of this patrol in the rapid detection of renewed infections at a previously infected site.

10.1073/pnas.1208927109

Cite

Citations (242)

CD28 plays a critical role in the segregation of PKCθ within the immunologic synapse

Proceedings of the National Academy of Sciences (2002)

Jianyong Huang Pei-Fen Lo Tomasz Żal Nicholas R. J. Gascoigne Bruce A. Smith

The signaling pathways that lead to the localization of cellular protein to the area of interaction between T cell and antigen-presenting cell and the mechanism by which these molecules are further sorted to the peripheral supramolecular activation cluster or central supramolecular activation cluster regions of the immunologic synapse are poorly understood. In this study, we investigated the functional involvement of CD28 costimulation in the T cell receptor (TCR)-mediated immunologic synapse formation with respect to protein kinase C (PKC)θ localization. We showed that CD3 crosslinking alone was sufficient to induce PKCθ capping in naïve CD4 + T cells. Studies with pharmacologic inhibitors and knockout mice showed that the TCR-derived signaling that drives PKCθ membrane translocation requires the Src family kinase, Lck, but not Fyn. In addition, a time course study of the persistence of T cell molecules to the immunologic synapse indicated that PKCθ, unlike TCR, persisted in the synapse for at least 4 h, a time that is sufficient for commitment of a T cell to cell division. Finally, by using TCR-transgenic T cells from either wild-type or CD28-deficient mice, we showed that CD28 expression was required for the formation of the mature immunologic synapse, because antigen stimulation of CD28 − T cells led to a diffuse pattern of localization of PKCθ and lymphocyte function-associated antigen-1 in the immunologic synapse, in contrast to the central supramolecular activation cluster localization of PKCθ in CD28 + T cells.

Immunological synapse

FYN

Jurkat cells

10.1073/pnas.142298399

Cite

Citations (142)

Regulation of T-cell activation and migration by the kinase TBK1 during neuroinflammation

Nature Communications (2015)

Jiayi Yu Xiaofei Zhou Mikyoung Chang Mako Nakaya Jae–Hoon Chang

Abstract Development of an immune or autoimmune response involves T-cell activation in lymphoid organs and subsequent migration to peripheral tissues. Here we show that T-cell-specific ablation of the kinase TBK1 promotes T-cell activation but causes retention of effector T cells in the draining lymph node in a neuroinflammatory autoimmunity model, experimental autoimmune encephalomyelitis (EAE). At older ages, the T-cell-conditional TBK1-knockout mice also spontaneously accumulate T cells with activated phenotype. TBK1 controls the activation of AKT and its downstream kinase mTORC1 by a mechanism involving TBK1-stimulated AKT ubiquitination and degradation. The deregulated AKT-mTORC1 signalling in turn contributes to enhanced T-cell activation and impaired effector T-cell egress from draining lymph nodes. Treatment of mice with a small-molecule inhibitor of TBK1 inhibits EAE induction. These results suggest a role for TBK1 in regulating T-cell migration and establish TBK1 as a regulator of the AKT-mTORC1 signalling axis.

TANK-binding kinase 1

10.1038/ncomms7074

Cite

Citations (102)

Expression of a second receptor rescues self-specific T cells from thymic deletion and allows activation of autoreactive effector function.

Proceedings of the National Academy of Sciences (1996)

Tomasz Żal Siegfried Weiß Andrew L. Mellor Brigitta Stockinger

Allelic exclusion at the T-cell receptor alpha chain locus is incomplete resulting in the generation of T cells that express two T-cell receptors. The potential involvement of such T cells in autoimmunity has been suggested [Padovan, E., Casorati, G., Dellabona, P., Meyer, S., Brockhaus, M. & Lanzavecchia, A. (1993) Science 262, 422-424; Heath, W. R. & Miller, J. F. A. P. (1993) J. Exp. Med. 178, 1807-1811]. Here we show that expression of a second T-cell receptor can rescue T cells with autospecific receptors from thymic deletion and allow their exit into the periphery. Dual receptor T cells, created by constitutive expression of two transgenic T-cell receptors on a Rag1-/- background, are tolerant to self by maintaining low levels of autospecific receptor, but selfreactive effector function (killing) can be induced through activation via the second receptor. This opens the possibility that T cells carrying two receptors in the periphery of normal individuals contain putatively autoreactive cells that could engage in autoimmune effector functions after recognition of an unrelated environmental antigen.

Allelic exclusion

Immune receptor

10.1073/pnas.93.17.9102

Cite

Citations (121)

Drosophila melanogaster as a model host to dissect the immunopathogenesis of zygomycosis

Proceedings of the National Academy of Sciences (2008)

Georgios Chamilos Russell E. Lewis Jianhua Hu Lianchun Xiao Tomasz Żal

Zygomycosis is an emerging frequently fatal opportunistic mycosis whose immunopathogenesis is poorly understood. We developed a zygomycosis model by injecting Drosophila melanogaster flies with a standardized amount of fungal spores from clinical Zygomycetes isolates to study virulence and host defense mechanisms. We found that, as opposed to most other fungi, which are nonpathogenic in D. melanogaster (e.g., Aspergillus fumigatus), Zygomycetes rapidly infect and kill wild-type flies. Toll-deficient flies exhibited increased susceptibility to Zygomycetes, whereas constitutive overexpression of the antifungal peptide Drosomycin in transgenic flies partially restored resistance to zygomycosis. D. melanogaster Schneider 2 phagocytic cells displayed decreased phagocytosis and caused less hyphal damage to Zygomycetes compared with that to A. fumigatus. Furthermore, phagocytosis-defective eater mutant flies displayed increased susceptibility to Zygomycetes infection. Classic enhancers of Zygomycetes virulence in humans, such as corticosteroids, increased iron supply, and iron availability through treatment with deferoxamine dramatically increased Zygomycetes pathogenicity in our model. In contrast, iron starvation induced by treatment with the iron chelator deferasirox significantly protected flies infected with Zygomycetes. Whole-genome expression profiling in wild-type flies after infection with Zygomycetes vs. A. fumigatus identified genes selectively down-regulated by Zygomycetes, which act in pathogen recognition, immune defense, stress response, detoxification, steroid metabolism, or tissue repair or have unknown functions. Our results provide insights into the factors that mediate host-pathogen interactions in zygomycosis and establish D. melanogaster as a promising model to study this important mycosis.

Zygomycosis

10.1073/pnas.0709578105

Cite

Citations (134)

A Conserved Motif in the ITK PH-Domain Is Required for Phosphoinositide Binding and TCR Signaling but Dispensable for Adaptor Protein Interactions

PLoS ONE (2012)

Nupura Hirve Roman M. Levytskyy Stéphanie Rigaud David M. Guimond Tomasz Żal

Binding of the membrane phospholipid phosphatidylinositol 3,4,5-trisphosphate (PIP3) to the Pleckstrin Homology (PH) domain of the Tec family protein tyrosine kinase, Inducible T cell Kinase (ITK), is critical for the recruitment of the kinase to the plasma membrane and its co-localization with the TCR-CD3 molecular complex. Three aromatic residues, termed the FYF motif, located in the inner walls of the phospholipid-binding pocket of the ITK PH domain, are conserved in the PH domains of all Tec kinases, but not in other PH-domain containing proteins, suggesting an important function of the FYF motif in the Tec kinase family. However, the biological significance of the FYF amino acid motif in the ITK-PH domain is unknown. To elucidate it, we have tested the effects of a FYF triple mutant (F26S, Y90F, F92S), henceforth termed FYF-ITK mutant, on ITK function. We found that FYF triple mutation inhibits the TCR-induced production of IL-4 by impairing ITK binding to PIP3, reducing ITK membrane recruitment, inducing conformational changes at the T cell-APC contact site, and compromising phosphorylation of ITK and subsequent phosphorylation of PLCγ1. Interestingly, however, the FYF motif is dispensable for the interaction of ITK with two of its signaling partners, SLP-76 and LAT. Thus, the FYF mutation uncouples PIP3-mediated ITK membrane recruitment from the interactions of the kinase with key components of the TCR signalosome and abrogates ITK function in T cells.

Pleckstrin homology domain

C2 domain

Protein kinase domain

10.1371/journal.pone.0045158

Cite

Citations (4)

OTUD7B controls non-canonical NF-κB activation through deubiquitination of TRAF3

Nature (2013)

Hongbo Hu George C. Brittain Jae‐Hoon Chang Nahum Puebla‐Osorio Jin Jin

10.1038/nature11831

Cite

Citations (191)