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Prostaglandin E2 and IL-23 interconnects STAT3 and RoRγ pathways to initiate Th17 CD4+ T-cell development during rheumatoid arthritis

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Abstract

Background

The chronic inflammation associated with rheumatoid arthritis (RA) leads to focal and systemic bone erosion of the joints resulting in a crippling disability. Recent reports indicate an increase in the incidence of RA in the coming years, placing a significant burden on healthcare resources. The incidence of RA is observed to be increasing with age and a significant proportion of those new cases will be aggressively erosive.

Findings

The altered physiology, due to immune disturbances, contributes towards RA pathogenesis. The imbalance of inflammatory cytokines and non-cytokine immune modulators such as prostaglandin E2 (PGE2) and IL-23-induced pathogenic IL-17, plays a crucial role in persistent inflammation and bone degradation during RA. However, the molecular mechanism of IL-23, a key cytokine, and PGE2 in the development and perpetuation of IL-17 producing effector Th17 cells is poorly understood.

Conclusion

This review focuses on research findings that provide insight into the contribution of PGE2 and IL-23 during the development of pathogenic Th17 cells. We also highlight the key transcriptional factors required for Th17 development and therapeutic strategies to disrupt the interaction between IL-23 and IL-17 to prevent the end-organ damage in RA.

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Acknowledgements

We thank the late Dr. Ramprasad VR Mula for his critical comments and insights into the article.

Funding

This work was supported by Chief Scientific Officer Funding for MS-Biomedical thesis from PCOM, American Heart Association award [11SDG5710004] and National Institute of Allergy and Infectious Diseases [1R03 AI128254-01A1] to R.S.

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Author notes

  1. Janaiya S. Samuels and Lauren Holland contributed equally.

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine-Georgia Campus, Room 3031, 625 Old Peachtree Road, NW, Suwanee, GA, 30024, USA

    Janaiya S. Samuels, Lauren Holland, María López, Keya Meyers, William G. Cumbie, Anna McClain, Aleksandra Ignatowicz, Daryllynn Nelson & Rangaiah Shashidharamurthy

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  1. Janaiya S. Samuels
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Contributions

JS, LH, equally contributed in collecting the data and drafting the manuscript. ML, KY, WC, AM collected the data and drafted the manuscript. AI and DN collected the data. RS designed and wrote the manuscript.

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Correspondence to Rangaiah Shashidharamurthy.

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Samuels, J.S., Holland, L., López, M. et al. Prostaglandin E2 and IL-23 interconnects STAT3 and RoRγ pathways to initiate Th17 CD4+ T-cell development during rheumatoid arthritis. Inflamm. Res. 67, 589–596 (2018). https://doi.org/10.1007/s00011-018-1153-8

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