Innate Lymphocytes: Protector or Foe?

October 18, 2016

Innate lymphocytes may have a role as disease targets in rheumatoid arthritis, psoriatic arthritis and/or inflammatory bowel disease, researchers say.

Proinflammatory innate lymphocytes are immune cells that may contribute to the development of autoimmune disease and as such, could possibly make ideal therapeutic targets, say researchers writing in Nature Reviews Rheumatology.

The role of innate lymphocytes is as protector, or disease causing, in immune-related disorders. They have roles in responding to antigen-specific autoantibodies and autoreactive T cells and in doing so, they can contribute to disease progression. Innate lymphocytes have also been shown to respond to biologic therapies prescribed in autoimmune diseases.

Proinflammatory mediators that are released by innate lymphocytes include IFNγ, TNF, IL‑17, IL‑23, granulocyte–macrophage colony-stimulating factor (GM-CSF) and IL‑1β. They can also release transforming growth factor-β (TGFβ), which can promote T helper type 17 (TH17) cell differentiation or have anti-inflammatory effects depending on which other cytokines are present.

The authors of the review, led by Mark A. Exley, Ph.D., of Harvard Medical School in Boston, outline several innate lymphocyte lineages that may have a role in rheumatoid arthritis, psoriatic arthritis and/or inflammatory bowel disease.

Natural killer (NK) cells belong to a group derived from lymphoid lineage, but do not undergo receptor arrangement. CD56 and CD16 NK cells, which can activate and inhibit NK cell receptors, IL-12 and IL-18, could have a possible role as a therapeutic target in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). CD56 NK cells are found in the synovial fluid of rheumatoid arthritis patients. “NK cells producing IL‑22 and TNF have also been found in the synovial fluid of patients with RA (and Lyme arthritis and PsA), where their numbers correlate with disease activity,” the reviewers wrote. But NK cells, in systemic lupus erythematosus (SLE) can show reduced cytotoxicity and less responsiveness, suggesting that NK cells may have disease-specific roles.

ILC cell subsets have roles in bridging innate and adaptive immunity. Type 1 ILCs might contribute to inflammatory bowel disease, the authors write, with IL-2 and IL-12 as the mechanisms of activation.

And, finally, MAIT cells, were also identified as having a possible role in rheumatoid arthritis with linkage to high levels of synovial fluid in RA joints. Some MAIT cells produce large amounts of mostly pro-inflammatory cytokines such as IFNγ and IL‑17.

“Innate lymphocytes represent alternative therapeutic targets in autoimmune diseases. We propose that innate lymphocyte subsets represent attractive targets in the context of autoimmune disease that could offer a therapeutic benefit with a favorable balance of efficacy and safety, which always presents a challenge in patients with autoimmune disease,” the authors wrote.

 

References:

Mark A. Exley, George C. Tsokos, et al. "What rheumatologists need to know about innate lymphocytes,"Nature Reviews Rheumatology. Sept. 2, 2016. doi:10.1038/nrrheum.2016.140