PKC-theta in regulatory and effector T-cell functions

Vedran Brezar, Sherry TU, Nabila Seddiki

Research output: Contribution to journalReview article

12 Citations (Scopus)

Abstract

One of the major goals in immunology research is to understand the regulatory mechanisms that underpin the rapid switch on/offof robust and efficient effector (Teffs) or regulatory (Tregs) T-cell responses. Understanding the molecular mechanisms underlying the regulation of such responses is critical for the development of effective therapies. T-cell activation involves the engagement of T-cell receptor and co-stimulatory signals, but the subsequent recruitment of serine/threonine-specific protein Kinase C-theta (PKC-¿) to the immunological synapse (IS) is instrumental for the formation of signaling complexes, which ultimately lead to a transcriptional network in T cells. Recent studies demonstrated that major differences between Teffs and Tregs occurred at the IS where its formation induces altered signaling pathways in Tregs. These pathways are characterized by reduced recruitment of PKC-¿, suggesting that PKC-¿ inhibits Tregs suppressive function in a negative feedback loop. As the balance of Teffs and Tregs has been shown to be central in several diseases, it was not surprising that some studies revealed that PKC-¿ plays a major role in the regulation of this balance. This review will examine recent knowledge on the role of PKC-¿ in T-cell transcriptional responses and how this protein can impact on the function of both Tregs and Teffs.
Original languageEnglish
Article number530
Pages (from-to)1-10
Number of pages10
JournalFrontiers in Immunology
Volume6
DOIs
Publication statusPublished - 2015

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Regulatory T-Lymphocytes
Protein Kinase C
Immunological Synapses
T-Lymphocytes
Gene Regulatory Networks
Protein-Serine-Threonine Kinases
T-Cell Antigen Receptor
Allergy and Immunology
Research
Proteins

Cite this

Brezar, Vedran ; TU, Sherry ; Seddiki, Nabila. / PKC-theta in regulatory and effector T-cell functions. In: Frontiers in Immunology. 2015 ; Vol. 6. pp. 1-10.
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PKC-theta in regulatory and effector T-cell functions. / Brezar, Vedran; TU, Sherry; Seddiki, Nabila.

In: Frontiers in Immunology, Vol. 6, 530, 2015, p. 1-10.

Research output: Contribution to journalReview article

TY - JOUR

T1 - PKC-theta in regulatory and effector T-cell functions

AU - Brezar, Vedran

AU - TU, Sherry

AU - Seddiki, Nabila

PY - 2015

Y1 - 2015

N2 - One of the major goals in immunology research is to understand the regulatory mechanisms that underpin the rapid switch on/offof robust and efficient effector (Teffs) or regulatory (Tregs) T-cell responses. Understanding the molecular mechanisms underlying the regulation of such responses is critical for the development of effective therapies. T-cell activation involves the engagement of T-cell receptor and co-stimulatory signals, but the subsequent recruitment of serine/threonine-specific protein Kinase C-theta (PKC-¿) to the immunological synapse (IS) is instrumental for the formation of signaling complexes, which ultimately lead to a transcriptional network in T cells. Recent studies demonstrated that major differences between Teffs and Tregs occurred at the IS where its formation induces altered signaling pathways in Tregs. These pathways are characterized by reduced recruitment of PKC-¿, suggesting that PKC-¿ inhibits Tregs suppressive function in a negative feedback loop. As the balance of Teffs and Tregs has been shown to be central in several diseases, it was not surprising that some studies revealed that PKC-¿ plays a major role in the regulation of this balance. This review will examine recent knowledge on the role of PKC-¿ in T-cell transcriptional responses and how this protein can impact on the function of both Tregs and Teffs.

AB - One of the major goals in immunology research is to understand the regulatory mechanisms that underpin the rapid switch on/offof robust and efficient effector (Teffs) or regulatory (Tregs) T-cell responses. Understanding the molecular mechanisms underlying the regulation of such responses is critical for the development of effective therapies. T-cell activation involves the engagement of T-cell receptor and co-stimulatory signals, but the subsequent recruitment of serine/threonine-specific protein Kinase C-theta (PKC-¿) to the immunological synapse (IS) is instrumental for the formation of signaling complexes, which ultimately lead to a transcriptional network in T cells. Recent studies demonstrated that major differences between Teffs and Tregs occurred at the IS where its formation induces altered signaling pathways in Tregs. These pathways are characterized by reduced recruitment of PKC-¿, suggesting that PKC-¿ inhibits Tregs suppressive function in a negative feedback loop. As the balance of Teffs and Tregs has been shown to be central in several diseases, it was not surprising that some studies revealed that PKC-¿ plays a major role in the regulation of this balance. This review will examine recent knowledge on the role of PKC-¿ in T-cell transcriptional responses and how this protein can impact on the function of both Tregs and Teffs.

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KW - Immune interventions

KW - Immune synapse

KW - PKC-θ

KW - Regulatory T cells

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