Innate immune cells, particularly macrophages and epithelial cells, play a key role in multiple layers of immune responses. Alarmins and pro-inflammatory cytokines from the IL (interleukin)-1 and TNF (tumour necrosis factor) families initiate the cascade of events by inducing chemokine release from bystander cells and by the up-regulation of adhesion molecules required for transendothelial trafficking of immune cells. Furthermore, innate cytokines produced by dendritic cells, macrophages, epithelial cells and innate lymphoid cells seem to play a critical role in polarization of helper T-cell cytokine profiles into specific subsets of Th1/Th2/Th17 effector cells or regulatory T-cells. Lastly, the innate immune system down-regulates effector mechanisms and restores homoeostasis in injured tissue via cytokines from the IL-10 and TGF (transforming growth factor) families mainly released from macrophages, preferentially the M2 subset, which have a capacity to induce regulatory T-cells, inhibit the production of pro-inflammatory cytokines and induce healing of the tissue by regulating extracellular matrix protein deposition and angiogenesis. Cytokines produced by innate immune cells represent an attractive target for therapeutic intervention, and multiple molecules are currently being tested clinically in patients with inflammatory bowel disease, rheumatoid arthritis, systemic diseases, autoinflammatory syndromes, fibrosing processes or malignancies. In addition to the already widely used blockers of TNFα and the tested inhibitors of IL-1 and IL-6, multiple therapeutic molecules are currently in clinical trials targeting TNF-related molecules [APRIL (a proliferation-inducing ligand) and BAFF (B-cell-activating factor belonging to the TNF family)], chemokine receptors, IL-17, TGFβ and other cytokines.
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Review Article|
January 14 2014
Cytokine networking of innate immunity cells: a potential target of therapy
Ilja Striz;
*Department of Clinical and Transplant Immunology, Institute for Clinical and Experimental Medicine, Videnska 1958/9 Prague, Czech Republic
†1st Medical Faculty, Charles University, Prague, Czech Republic
Correspondence: Professor Ilja Striz (email [email protected]).
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Eva Brabcova;
Eva Brabcova
*Department of Clinical and Transplant Immunology, Institute for Clinical and Experimental Medicine, Videnska 1958/9 Prague, Czech Republic
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Libor Kolesar;
Libor Kolesar
*Department of Clinical and Transplant Immunology, Institute for Clinical and Experimental Medicine, Videnska 1958/9 Prague, Czech Republic
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Alena Sekerkova
Alena Sekerkova
*Department of Clinical and Transplant Immunology, Institute for Clinical and Experimental Medicine, Videnska 1958/9 Prague, Czech Republic
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Publisher: Portland Press Ltd
Received:
August 16 2013
Revision Received:
October 18 2013
Accepted:
October 22 2013
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2014 Biochemical Society
2014
Clin Sci (Lond) (2014) 126 (9): 593–612.
Article history
Received:
August 16 2013
Revision Received:
October 18 2013
Accepted:
October 22 2013
Citation
Ilja Striz, Eva Brabcova, Libor Kolesar, Alena Sekerkova; Cytokine networking of innate immunity cells: a potential target of therapy. Clin Sci (Lond) 1 May 2014; 126 (9): 593–612. doi: https://doi.org/10.1042/CS20130497
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