Resolving Inflammation: Research on Signals & Mediators Continues to Advance

The cytokine and cellular pathways triggering arthritis are well known, Dr. Schett said, but those responsible for inflammation resolution are not.^10-12

In a 2018 mice study co-authored by Dr. Schett, researchers identified IL-9-producing type 2 innate lymphoid cells (ILC2s) as a molecular and cellular pathway that manages resolution of chronic inflammation. The researchers found the absence of IL-9 impaired ILC2 proliferation, and activation of regulatory T cells resulted in chronic arthritis with cartilage destruction and bone loss.

“In contrast,” the researchers wrote, “Treatment with IL-9 promoted ILC2-dependent Treg activation and effectively induced resolution of inflammation and protection of bone. Patients with rheumatoid arthritis in remission exhibited high numbers of IL-9⁺ ILC2s in joints and the circulation. Hence, fostering IL-9-mediated ILC2 activation may offer a novel therapeutic approach inducing resolution of inflammation rather than suppression of inflammatory responses.”¹³

“[Although] IL-9 is still a black sheep,” said Dr. Schett, “it’s being recognized as a very special sheep. That’s because IL-9 is the only cytokine that triggers the resolution of inflammation.”

Mike Fillon is a healthcare writer living in the Atlanta area.

References

1. Serhan CN, Levy BD. Resolvins in inflammation: Emergence of the pro-resolving superfamily of mediators. J Clin Invest. 2018 Jul 2;128(7):2657–2669.
2. Serhan CN, Savill J. Resolution of inflammation: The beginning programs the end. Nat Immunol. 2005 Dec;6(12):1191–1197.
3. Serhan CN. Novel lipid mediators and resolution mechanisms in acute inflammation: To resolve or not? Am J Pathol. 2010 Oct;177(4):1576–1591.
4. Serhan C, Chiang N, Dalli, J. The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution. Semin Immunol. 2015 May;27(3):200–2
5. Pavlov VA, Tracey KJ. Neural regulation of immunity: Molecular mechanisms and clinical translation. Nat Neurosci. 2017 Feb;20(2):156–166.
6. Mirakai V, Dalli J, Granja T, et al. Vagus nerve controls resolution and pro-resolving mediators of inflammation. J Exp Med. 2014 Jun 2;211(6):1037–1048.
7. Serhan C, de la Rosa X, Jouvene X, et al. Cutting edge: Human vagus produces specialized proresolving mediators of inflammation with electrical stimulation reducing proinflammatory eicosanoids. J Immunol. 2018 Dec 1;201(11):3161–
8. Luo X, Gu Y, Tao X, et. al. Resolvin D5 inhibits neuropathic and inflammatory pain in male but not female mice: Distinct actions of D-series resolvins in chemotherapy-induced peripheral neuropathy. Front Pharmacol. 2019 Jul 5;10:745.
9. Goswami R, Kaplan MH. A brief history of IL-9. J Immunol. 2011 Mar 15;186(6):3283–3288.
10. Rauber S, Luber M, Weber S, et al. Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells. Nat Med. 2017 Aug;23(8):938–944.
11. McInnes I, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011 Dec 8;365(23):2205–2219.
12. Schett G, Elewaut D, McInnes IB, et al. How cytokine networks fuel inflammation: Toward a cytokine-based disease taxonomy. Nat Med. 2013 Jul;19(7):822–824.
13. Omata Y, Frech M, Primbs T, et al. Group 2 innate lymphoid cells attenuate inflammatory arthritis and protect from bone destruction in mice. Cell Rep. 2018 Jul 3;24(1):169–180.