Article
γδ T cells as prominent source of IL-17 in SJIA
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Published: | September 1, 2015 |
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Introduction: Systemic Juvenile Idiopathic Arthritis (SJIA) comprises about 6-20% of all Juvenile Idiopathic Arthritis (JIA) patients and has an incidence of 0.4-0.9 per 100.000 children/year. It presents with arthritis, high spiking fever, erythematous rash, lymphadenopathy, hepatosplenomegaly and serositis. The disease is currently considered to follow a biphasic course in which the initial systemic phase is driven by innate immune mechanisms with IL-1 as key cytokine, while the second more destructive phase appears to be dominated by adaptive immunity and cytokines such as IL-6 or IL-17.
While TH 17 cells are suggested to be enriched in SJIA, the role of γδ T cells as an important IL-17 source at the crossroads between innate and adaptive immunity is poorly defined.
Methods: Whole blood cells from 21 SJIA, 8 Familial Mediterranean Fever (FMF; as systemic inflammation control group), and 13 pediatric health control samples were left untreated or were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin in presence of protein transport inhibitors (brefeldin A and monensin). Unstimulated as well as stimulated cells were stained for expression of CD3, CD4, TCRγδ, IL-17, IL-22 and INFγ and analyzed by flow cytometry.
Results: Although significantly increased numbers of CD3+CD4+ T cells were found in SJIA as well as in FMF patient samples compared to healthy controls, cells expressing TCRγδ are significantly under-represented in particularly SJIA patients’ whole blood. Patients’ follow-up samples suggest γδ T cell levels to be reduced in active disease and to re-establish during remission. Yet, although fewer in number, SJIA γδ T cells express high levels of particularly IL-17 compared to healthy controls. γδ T cellular IL-17 production tends to be even further increased in active SJIA, while levels in quiescent disease still remain significantly elevated.
Conclusion: Albeit the overall frequency of γδ T cells is particularly reduced in SJIA, these cells pose a prominent source for IL-17 in active but also quiescent disease. As the reduction in γδ T cell counts appears to negatively correlate with disease activity, monitoring these cell counts in peripheral blood may serve as marker in following patients’ therapy and eventually supports predicting disease flares.