Projektdetails
Abstract
NOD‐like receptor family pyrin domain containing‐1 and ‐3 proteins (NLRP1 and
NLRP3) are important components of macromolecular complexes called inflammasomes.
Inflammasome activation induces caspase‐1‐mediated cleavage and activation of pro‐
IL‐1β and pro‐IL‐18. NLRP1 is expressed in natural killer (NK), T, and myeloid cells, and
is significantly involved in the pathogenicity of anthrax lethal toxin. However, its
functional role in these immune cells is still poorly understood. In contrast, NLRP3 is
primarily expressed in myeloid cells and activated by a variety of signals. NLRP3
hyperactivation is associated with pathological processes, such as autoimmune and
inflammatory diseases but also carcinogenesis and tumor progression. The role of
NLRP3 apart from its function in the inflammasome has not been investigated yet.
Remarkably, Nlrp3‐deficient mice are more resistant to tumor metastasis through a
mechanism that involves altered myeloid differentiation and enhanced NK cell
recruitment. Hitherto the mechanistic details of this effect have not been studied.
Additionally, it was suggested that NLRP3 might have an impact on T helper cell
polarization under specific experimental conditions, which is independent of its wellestablished
function in the inflammasome complex.
In this project I aim to study the relevance of NLRP3 (i) in T cell differentiation, T
cell priming by antigen‐presenting cells and the generation of T cell effector functions
and (ii) in NK cell survival and chemotaxis. The second part of the project addresses the
question, whether NLRP1 shares a similar function with NLRP3 in the fight against
bacterial infections and tumor development. This work will give new insights in the role
of NOD‐like receptors in the development of innate and adaptive immune cell responses.
NLRP3) are important components of macromolecular complexes called inflammasomes.
Inflammasome activation induces caspase‐1‐mediated cleavage and activation of pro‐
IL‐1β and pro‐IL‐18. NLRP1 is expressed in natural killer (NK), T, and myeloid cells, and
is significantly involved in the pathogenicity of anthrax lethal toxin. However, its
functional role in these immune cells is still poorly understood. In contrast, NLRP3 is
primarily expressed in myeloid cells and activated by a variety of signals. NLRP3
hyperactivation is associated with pathological processes, such as autoimmune and
inflammatory diseases but also carcinogenesis and tumor progression. The role of
NLRP3 apart from its function in the inflammasome has not been investigated yet.
Remarkably, Nlrp3‐deficient mice are more resistant to tumor metastasis through a
mechanism that involves altered myeloid differentiation and enhanced NK cell
recruitment. Hitherto the mechanistic details of this effect have not been studied.
Additionally, it was suggested that NLRP3 might have an impact on T helper cell
polarization under specific experimental conditions, which is independent of its wellestablished
function in the inflammasome complex.
In this project I aim to study the relevance of NLRP3 (i) in T cell differentiation, T
cell priming by antigen‐presenting cells and the generation of T cell effector functions
and (ii) in NK cell survival and chemotaxis. The second part of the project addresses the
question, whether NLRP1 shares a similar function with NLRP3 in the fight against
bacterial infections and tumor development. This work will give new insights in the role
of NOD‐like receptors in the development of innate and adaptive immune cell responses.
Kurztitel | NLRP1 und NLRP3 in T und NK Zell-vermittelter Immunität |
---|---|
Status | Abgeschlossen |
Tatsächlicher Beginn/ -es Ende | 1/03/15 → 31/03/18 |
Projektbeteiligte
- Universität Wien (Leitung)
- Veterinärmedizinische Universität Wien
- Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute
Schlagwörter
- Inflammasome
- Immunology
- Natural Killer cells
- T cells
- Tumor immunology
- Bacterial infections