Restoration of NK Cell Cytotoxic Function With Elotuzumab and Daratumumab Promotes Elimination of Circulating Plasma Cells in Patients With SLE

Autor: Camillo Ribi, Madeleine Suffiotti, Denis Comte, Morgane Humbel, Florence Bellanger, Alice Horisberger, Craig Fenwick, Natalia Fluder
Jazyk: angličtina
Rok vydání: 2021
Předmět:
lcsh:Immunologic diseases. Allergy
0301 basic medicine
Adult
Male
medicine.medical_treatment
Plasma Cells
Immunology
CD150/SLAMF1 receptor
CD319/SLAMF7/CS1
CD38
NK cells
SLAMF
daratumumab
elotuzumab
systemic lupus erythematosus (SLE)
Antibodies
Monoclonal
Humanized
03 medical and health sciences
0302 clinical medicine
immune system diseases
medicine
Immunology and Allergy
Cytotoxic T cell
Humans
Lupus Erythematosus
Systemic
skin and connective tissue diseases
B cell
Aged
Original Research
030203 arthritis & rheumatology
business.industry
SLAMF7
Circulating Plasma Cell
Degranulation
Antibodies
Monoclonal
Recovery of Function
Middle Aged
Acquired immune system
3. Good health
Killer Cells
Natural
030104 developmental biology
Cytokine
medicine.anatomical_structure
Female
lcsh:RC581-607
business
Zdroj: Frontiers in immunology, vol. 12, pp. 645478
Frontiers in Immunology
Frontiers in Immunology, Vol 12 (2021)
Popis: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by multiple cellular and molecular dysfunctions of the innate and adaptive immunity. Cytotoxic function of NK cells is compromised in patients with SLE. Herein, we characterized the phenotypic alterations of SLE NK cells in a comprehensive manner to further delineate the mechanisms underlying the cytotoxic dysfunction of SLE NK cells and identify novel potential therapeutic targets. Therefore, we examined PBMC from SLE patients and matched healthy controls by single-cell mass cytometry to assess the phenotype of NK cells. In addition, we evaluated the cell function of NK cells (degranulation and cytokine production) and the killing of B cell subpopulations in a B cell-NK cell in vitro co-culture model. We found that SLE NK cells expressed higher levels of CD38 and were not able to adequately upregulate SLAMF1 and SLAMF7 following activation. In addition, ligation of SLAMF7 with elotuzumab or of CD38 with daratumumab on SLE NK cells enhanced degranulation of both healthy and SLE NK cells and primed them to kill circulating plasma cells in an in vitro co-culture system. Overall, our data indicated that dysregulated expression of CD38, SLAMF1 and SLAMF7 on SLE NK cells is associated with an altered interplay between SLE NK cells and plasma cells, thus suggesting their contribution to the accumulation of (auto)antibody producing cells. Accordingly, targeting SLAMF7 and CD38 may represent novel therapeutic approaches in SLE by enhancing NK cell function and promoting elimination of circulating plasma cell.
Databáze: OpenAIRE
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