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oai:repisalud.isciii.es:20.500.12105/167632024-09-27T09:35:57Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Sánchez-Cerrillo, Ildefonso author Calzada-Fraile, Diego author Triguero-Martínez, Ana author Calvet-Mirabent, Marta author Popova, Olga author Delgado-Arévalo, Cristina author Valdivia-Mazeyra, Mariel author Ramírez-Huesca, Marta author Vázquez de Luis, Enrique author Benguría, Alberto author Aceña-Gonzalo, Teresa author Moreno-Vellisca, Roberto author Adrados de Llano, Magdalena author de la Fuente, Hortensia author Tsukalov, Ilya author Delgado-Wicke, Pablo author Fernández-Ruiz, Elena author Roy-Vallejo, Emilia author Tejedor-Lázaro, Reyes author Ramiro, Almudena R author Iborra, Salvador author Sánchez-Madrid, Francisco author Dopazo, Ana author Álvaro, Isidoro González author Castañeda, Santos author Martin-Gayo, Enrique author 2023-12-01 Primary Sjögren's syndrome (pSS) is an inflammatory autoimmune disorder largely mediated by type I and II interferon (IFN). The potential contribution of innate immune cells, such as natural killer (NK) cells and dendritic cells (DC), to the pSS pathology remains understudied. Here, we identified an enriched CD16+ CD56hi NK cell subset associated with higher cytotoxic function, as well as elevated proportions of inflammatory CD64+ conventional dendritic cell (cDC2) subtype that expresses increased levels of MICa/b, the ligand for the activating receptor NKG2D, in pSS individuals. Circulating cDC2 from pSS patients efficiently induced activation of cytotoxic NK cells ex vivo and were found in proximity to CD56+ NK cells in salivary glands (SG) from pSS patients. Interestingly, transcriptional activation of IFN signatures associated with the RIG-I/DDX60 pathway, IFN I receptor, and its target genes regulate the expression of NKG2D ligands on cDC2 from pSS patients. Finally, increased proportions of CD64hi RAE-1+ cDC2 and NKG2D+ CD11b+ CD27+ NK cells were present in vivo in the SG after poly I:C injection. Our study provides novel insight into the contribution and interplay of NK and cDC2 in pSS pathology and identifies new potential therapy targets. EMBO J. 2023 Dec 1;42(23):e113714. 10.15252/embj.2023113714 1460-2075 The EMBO journal 37916875 http://hdl.handle.net/20.500.12105/16763 MICa/b-dependent activation of natural killer cells by CD64+ inflammatory type 2 dendritic cells contributes to autoimmunity.