Author:
Agrez Michael,Rzepecka Justyna,Turner Darryl,Knox Gavin,Chandler Christopher,Howard Christopher B.,Fletcher Nicholas,Thurecht Kristofer,Parker Stephen,Gooding Hayley,Gallagher Laura
Abstract
AbstractT cell-dendritic cell (DC) interactions contribute to reciprocal stimulation leading to DC maturation that results in production of interleukin-12 (IL-12) and interferon-gamma (IFN-γ). Both cytokines have been implicated in autoimmune diseases while being necessary for effective immune responses against foreign antigens. We describe a lipidic peptide,designated IK14004, that modifies crosstalk between T cells and DCs resulting in suppression of IL-12p40/IFN-γ production. T cell production of interleukin-2 (IL-2) and IFN-γ is uncoupled and IL-12p70 production is enhanced. IK14004 induces expression of activating co-receptors in CD8+ T cells and increases the proportion of Foxp3-expressing CD4+ T regulatory cells. The potential for IK14004 to impact on signalling pathways required to achieve a balanced immune response upon stimulation of DCs and T cells is highlighted. This novel compound provides an opportunity to gain further insights into the complexity of T cell-DC interactions relevant to autoimmunity associated with malignancies and may have therapeutic benefit.
Publisher
Springer Science and Business Media LLC
Reference97 articles.
1. Ma, Q. et al. Autoimmune comorbidities in patients with metastatic melanoma: A retrospective analysis of US claims data. BMC Cancer 18, 145 (2018).
2. Valencia, J. C. et al. Autoimmunity and cancer, the paradox comorbidities challenging therapy in the context of preexisting autoimmunity. J. Interferon Cytokine Res. 39, 72–84 (2019).
3. Kumar, P., Bhattacharya, P. & Prabhakar, B. S. A comprehensive review on the role of co-signaling receptors and Treg homeostasis in autoimmunity and tumor immunity. J. Autoimmun. 95, 77–99 (2018).
4. Pollard, K. M., Cauvi, D. M., Toomey, C. B., Morris, K. V. & Kono, D. H. Interferon-γ and systemic autoimmunity. Discov. Med. 16, 123–131 (2013).
5. Cooper, A. M. & Khader, S. A. IL-12p40: An inherently agonistic cytokine. Trends Immunol. 28, 33–38 (2007).
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