Rare Lymphocyte May Be Effective in Treatment During Onset of Inflammatory Arthritis

Group 2 innate lymphoid cells (ILC2s), a rare form of lymphocyte that defend the body from pathogens, may have immune-regulatory functions in rheumatoid arthritis (RA) and play a key role in the development of inflammatory arthritis, according to immunologists at Friedrich-Alexander-Universität Erlangen-Nürnberg.

A recent study, published by Cell Reports, investigated the different ILC2 gain- and loss-of-function models during inflammatory arthritis. The researchers were able to demonstrate the number of ILC2 in the peripheral blood and in the joints of patients with RA was significantly higher than in healthy people.

In addition, when the researchers genetically reduced the number of immune cells—which exacerbated the progression of the disease later on—and increased the number of ILC2 during therapy, the arthritis was significantly reduced during the early stages of the disease, explained the authors. Despite this result, the study emphasized that this may not be effective for curing patients who already have inflammatory arthritis.

“In our current study, we specifically examined the role of ILC2s in the early stage of rheumatoid arthritis,” Mario Zaiss, PhD, Department of Medicine 3, Rheumatology and Immunology at Universitätsklinikum Erlangen, said in a statement. “There is no doubt that ILC2 has a regulatory effect during the early stage of arthritis. However, any treatment must start before the onset of the disease — transferring ILC2 later on does not improve symptoms.”

The researchers were able to demonstrate that ILC2 numbers were increased both in patients with RA and inflammatory arthritis mouse models. The study explained that in 2 settings of genetically reduced ILC2 numbers, arthritis was worsened, while therapeutic enhancement of ILC2 number significantly reduced arthritis.

“This regulatory action of ILC2s was dependent on their capacity to secret IL-4/13, as IL4/13^-/- ILC2s failed to attenuate arthritis after adoptive cell transfer. Mechanistically, ILC2-derived IL-4/13 significantly suppressed IL-1b section by macrophages, and it was shown that both IL-1b and macrophages are key players driving early clinical symptoms in SIA [serum-induced arthritis] and RA,” the authors explained. “This mechanism was critical only during the initiation phase of arthritis, as therapeutically adoptive ILC2 transfer at later time points also failed to attenuate arthritis.”

Overall, the results reveal that ILC2s have immune-regulatory functions in arthritis. The authors suggested that this research could form the basis for new approaches for treating arthritis, since enhancement of ILC2 numbers may act as a method to effectively block the development of inflammatory arthritis. However, further research is necessary to find safe methods of increasing the number of ILC2 in the body and to find new methods of detecting signs of arthritis before the onset so ILC2s can be used as a treatment.

Reference

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;24(1):169-180. doi: 10.1016/j.celrep.2018.06.005.