Neutrophils control autoreactive Th17 responses in spondyloarthritis

Autor: Kofi N Asare-Konadu, Emily E Vance, Rouhin Sen, Liron Caplan, Holly L. Rosenzweig, Ruth J Napier
Rok vydání: 2022
Předmět:
Zdroj: The Journal of Immunology. 208:108.16-108.16
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.208.supp.108.16
Popis: Spondylarthritis (SpA) refers to a group of autoimmune diseases characterized by inflammation of the spine (spondylitis) and joints (arthritis) including ankylosing spondylitis and psoriatic arthritis. Genetic studies suggest that autoreactive Th17 cells drive SpA pathogenesis and in support IL-17 blockade in the clinic moderates symptoms. Although Th17 responses appear to be key in driving symptomatic disease, less is understood of the underlying innate cellular mechanisms that contribute to the initiation of pathogenic T cells. Upon analysis of SpA patient cell blood count data (1,497 events) we discovered a positive correlation between the absolute number of neutrophils and disease severity. Thus, we sought to determine how dysregulated neutrophil responses might control autoreactive Th17 responses using an experimental model of SpA (SKG mice). SKG mice have a point mutation in Zap70 resulting in autoreactive Th17 cells that cause arthritis and spondylitis. When SKG splenocyte cultures were treated with monoclonal antibodies to CD3 and simultaneously co-incubated with autologous neutrophils for 72h we detected increased T cell activation status (CD69 expression) and production of IL-17 but not IFNγ compared to media only (no neutrophils) controls. Neutrophil-deplete SKG mice had reduced autoreactive Th17 responses and delayed onset of arthritis compared to neutrophil-replete controls, supporting a role for neutrophils in promoting autoreactive Th17 responses and the induction of disease. In conclusion our data reveal a role for neutrophils in pathogenesis of SpA, indicating that neutrophil modulating drugs could be considered as a future treatment strategy for SpA. Supported by grants from VA (CDA-2 IK2BX004523 and Merit I01BX002180) and NIH (R01 EY025250)
Databáze: OpenAIRE
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