Aberrant Naive CD4 –Positive T Cell Differentiation in Systemic Juvenile Idiopathic Arthritis Committed to B Cell Help
Authors' conclusion
In the pathogenesis of systemic JIA, skewing of naive T helper cell differentiation toward a Tfh/Tph cell phenotype may represent an echo of autoimmunity
Study context
- Population
- Patients with sJIA and healthy controls; naive T helper cells cultured under Th1, Th17 and Tfh/T peripheral helper (Tph)-polarizing conditions, partly cocultured with allogenic memory B cells
- Participants
- 171 vs 72
- Comparison
- sJIA patients vs healthy controls
- sJIAn = 171
- Healthy controlsn = 72reference
Methodological detailsin vitro and ex vivo analyses, retrospective RNA profiling
- In vitro and ex vivo analyses
- Retrospective RNA profiling
Main finding
As reported in the abstract
- Th1 differentiation of sJIA naive T helper cells gave low IFNγ and eomesodermin expression, associated in part with disease duration
- Developing Th1 cells in sJIA produced elevated IL-21, negatively correlated with IFNγ and eomesodermin expression
- IL-21 with PD-1, ICOS and CXCR5 expression induced sJIA naive T helper cells to polarize toward a Tfh/Tph phenotype (in vitro and ex vivo)
- Bcl-6 overexpressed specifically in sJIA (whole-blood RNA-sequencing)
- Stimulated sJIA naive T helper cells promoted B cell plasmablast generation
- IgG self-antigen reactivity profiles of sJIA differed from healthy controls
Original publication
Aberrant Naive CD4 –Positive T Cell Differentiation in Systemic Juvenile Idiopathic Arthritis Committed to B Cell Help. Arthritis Rheumatol. Published 17 March 2023. doi:10.
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