Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells

Nature Medicine 2017, vol 23, p938

by Andreas Ramming from the Department of Internal Medicine at the Friedrich Alexander University in Germany

Abstract: Inflammatory diseases such as arthritis are chronic conditions that fail to resolve spontaneously. While the cytokine and cellular pathways triggering arthritis are well defined, those responsible for the resolution of inflammation are incompletely characterized. Here we identified interleukin (IL)-9-producing type 2 innate lymphoid cells (ILC2s) as the mediators of a molecular and cellular pathway that orchestrates the resolution of chronic inflammation. In mice, the absence of IL-9 impaired type 2 innate lymphoid cell proliferation and activation of regulatory T (Treg) cells, resulted in chronic arthritis with excessive cartilage destruction and bone loss. In contrast, treatment with IL-9 promoted type 2 innate lymphoid cell-dependent regulatory T cell activation and effectively induced resolution of inflammation and protection of bone. Patients with rheumatoid arthritis in remission exhibited high numbers of IL-9+ type 2 innate lymphoid cells in joints and the circulation. Hence, fostering IL-9-mediated type 2 innate lymphoid cell activation may offer a novel therapeutic approach inducing resolution of inflammation rather than suppression of inflammatory responses.

Key points from the Intro and Conclusion:

* Reversal of inflammation is incompletely understood

* Chronic inflammatory diseases include:

* Arthritis

* Alzheimers

* Asthma

* Atherosclerosis

* Crohn’s

* Colitis

* Irritable bowel syndrome

* Ulcerative colitis

* Current arthritis treatments include lifelong immunosuppressive treatment

* Current treatments strategies seek to prevent further inflammation instead of promoting its reversal

* They identified the cytokine, IL-9, and type 2 innate lymphoid cells, that produce IL-9, are responsible for reversing arthritis in a mouse animal model.

* They did this by using a mouse model where you can give the mouse a shot and it will develop arthritis, which then goes away spontaneously.

* This study is a great example of how to identify a new therapeutic pathway. They were very thorough.

* They compared their results in mice with synovial tissue of humans with rheumatoid arthritis and found similar correlation of IL-9 and type 2 innate lymphoid cell concentrations

* Final lines from their conclusions: These findings are remarkable, as resolution of inflammation has thus far been preferentially attributed to lipid mediators such as resolving and little was known about innate/adaptive immune system interactions in orchestrating the resolution process. IL-9 and the function of type 2 innate lymphoid cells in this process provide strong support for the existence of immune pathways that primarily foster the resolution of inflammation and restore immune homeostasis in chronic inflammatory diseases.

Dinner part tag line: I heard that researchers figured out a way to treat arthritis by reversing the disease, instead of just preventing it from progressing further. They said this could have broad implications for other inflammation diseases like heart disease, inflammatory bowel diseases, and alzheimers disease.

Business perspective:

* Interesting mechanistic research will still require several more years before an initial therapeutic will even be tested in the lab. I’m discussing this paper more because of my general interest in reversing inflammatory diseases than for its potential business applications