Figure 1.

NK cell involvement in autoimmune inflammatory diseases. NK cells exacerbate RA by secreting soluble mediators such as (a) M‐CSF and RANKL that drive the differentiation of bone‐eroding osteoclasts and (b) GM‐CSF that promotes the production of pro‐inflammatory mediators by joint‐infiltrating neutrophils. (c) NK cells do not appear to play a dominant role in MS but boosting their cytotoxic function with anti‐NKG2A may eliminate encephalitogenic Th17 cells and alleviate disease in the EAE model. (d) NK cells may promote SLE through their interaction with pDCs via LFA‐1 and DNAM‐1 that enhances the production of cytokines and chemokines such as IFN‐α, IFN‐γ, TNF‐α, IL‐6, IL‐8, CCL3 and CCL4. NK cells are also found in kidney of lupus nephritis patients but it remains unclear if NK cells and their cytokine dysfunction contribute to tissue pathology. (e) NK cells could contribute to the generation of autoantigens through excessive killing of CV‐B4‐infected pancreatic β islets. However, other functions of NK cells such as IFN‐γ production remain unclear and future studies are required to capture phenotypic and functional diversity of NK cells in both CV‐B4‐associated and sterile T1DM subtypes. (f) Alveolar NK cells are thought to give rise to autoantigens such as histidyl tRNA synthetase following respiratory insults in anti‐synthetase syndrome. Future studies are needed to evaluate whether similar numerical and functional changes in NK cells occur in the discrete subtype of IIM.