NK cell characteristics in AIDs
| Disease . | Circulating NK cells . | Tissue NK cells . | Predominant phenotype . | Activation/functional status . | Protective mechanisms . | Detrimental effects . |
|---|---|---|---|---|---|---|
| SLE | ↓ | ↑ (kidneys, glomeruli) | CD56bright (blood) | Activated phenotype, upregulation of NCRs; downregulation of CD16 and KIRs (blood); upregulation of MICA (kidneys); reduced cytotoxicity; increased IFN-γ production | Not well defined | Tissue-resident NKp46+ ILC1s amplify kidney inflammation through GM-CSF production |
| RA | ↑ | ↑ (synovial fluid) | CD56bright (synovial fluid) | Activated phenotype; reduced cytotoxicity; increased IFN-γ production (synovial NK cells) | Not well defined | Likely promotes synovial inflammation through IFN-γ and TNF-α; osteoclastogenesis and bone destruction via RANKL and M-CSF expression; exacerbates inflammation through GM-CSF production |
| pSS | ↓ | ↑ (salivary glands) | CD56bright (blood) | IFN-γ secretion (via interaction with B7-H6 expressed on salivary gland epithelial cells) | Tissue-resident NK shield target cells from T cell–mediated cytotoxicity | NK infiltration correlates with glandular inflammation; contributes to ectopic lymphoid structures formation; amplifies autoimmune responses in the glands via IFN-γ production |
| SSc | Debated/vary with stage | Not well defined | Not well defined | Not well defined | Not well defined | Not well defined |
| T1D | ↓ | ↑ (pancreatic islets) | | Activated phenotype, spontaneous IFN-γ at early stages; dysfunctional state at later stages | Secretion of immunosuppressive cytokines and killing of autoreactive T cells | Promotes adaptive autoimmune response and β cell destruction through IFN-γ production and NKp46-dependent cytotoxicity |
| Disease . | Circulating NK cells . | Tissue NK cells . | Predominant phenotype . | Activation/functional status . | Protective mechanisms . | Detrimental effects . |
|---|---|---|---|---|---|---|
| SLE | ↓ | ↑ (kidneys, glomeruli) | CD56bright (blood) | Activated phenotype, upregulation of NCRs; downregulation of CD16 and KIRs (blood); upregulation of MICA (kidneys); reduced cytotoxicity; increased IFN-γ production | Not well defined | Tissue-resident NKp46+ ILC1s amplify kidney inflammation through GM-CSF production |
| RA | ↑ | ↑ (synovial fluid) | CD56bright (synovial fluid) | Activated phenotype; reduced cytotoxicity; increased IFN-γ production (synovial NK cells) | Not well defined | Likely promotes synovial inflammation through IFN-γ and TNF-α; osteoclastogenesis and bone destruction via RANKL and M-CSF expression; exacerbates inflammation through GM-CSF production |
| pSS | ↓ | ↑ (salivary glands) | CD56bright (blood) | IFN-γ secretion (via interaction with B7-H6 expressed on salivary gland epithelial cells) | Tissue-resident NK shield target cells from T cell–mediated cytotoxicity | NK infiltration correlates with glandular inflammation; contributes to ectopic lymphoid structures formation; amplifies autoimmune responses in the glands via IFN-γ production |
| SSc | Debated/vary with stage | Not well defined | Not well defined | Not well defined | Not well defined | Not well defined |
| T1D | ↓ | ↑ (pancreatic islets) | | Activated phenotype, spontaneous IFN-γ at early stages; dysfunctional state at later stages | Secretion of immunosuppressive cytokines and killing of autoreactive T cells | Promotes adaptive autoimmune response and β cell destruction through IFN-γ production and NKp46-dependent cytotoxicity |