Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata.
Rimma Laufer BritvaAviad KerenMarta BertoliniYehuda UllmannRalf PausAmos GilharPublished in: eLife (2023)
Here, we have explored the involvement of innate lymphoid cells-type 1 (ILC1) in the pathogenesis of alopecia areata (AA), because we found them to be significantly increased around lesional and non-lesional HFs of AA patients. To further explore these unexpected findings, we first co-cultured autologous circulating ILC1-like cells (ILC1lc) with healthy, but stressed, organ-cultured human scalp hair follicles (HFs). ILClc induced all hallmarks of AA ex vivo: they significantly promoted premature, apoptosis-driven HF regression (catagen), HF cytotoxicity/dystrophy, and most important for AA pathogenesis, the collapse of the HFs physiological immune privilege. NKG2D-blocking or IFNγ-neutralizing antibodies antagonized this. In vivo, intradermal injection of autologous activated, NKG2D+/IFNγ-secreting ILC1lc into healthy human scalp skin xenotransplanted onto SCID/beige mice sufficed to rapidly induce characteristic AA lesions. This provides the first evidence that ILC1lc, which are positive for the ILC1 phenotype and negative for the classical NK markers, suffice to induce AA in previously healthy human HFs ex vivo and in vivo, and further questions the conventional wisdom that AA is always an autoantigen-dependent, CD8 +T cell-driven autoimmune disease.
Keyphrases
- endothelial cells
- nk cells
- immune response
- induced pluripotent stem cells
- high glucose
- pluripotent stem cells
- end stage renal disease
- bone marrow
- mass spectrometry
- chronic kidney disease
- ejection fraction
- induced apoptosis
- multiple sclerosis
- heart failure
- stem cells
- early onset
- prognostic factors
- patient reported outcomes
- drug induced
- adipose tissue
- mesenchymal stem cells
- liquid chromatography
- signaling pathway
- newly diagnosed
- atrial fibrillation
- insulin resistance
- tandem mass spectrometry
- high fat diet induced
- wild type