Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Role of IL-1b in the Development of Human TH17 Cells: Lesson from Patients Carrying NLPR3 Gene Mutations.
Lasiglie, Denise, Traggiai, Elisabetta, Penco, Federica, Federici, Silvia, Accogli, Andrea, Buoncompagni, Antonella, Martini, Alberto
Interleukin 17 (IL-17)-producing CD4+ helper T cells (Th-17) represents a lineage of effectors CD4 T cells abundant at mucosal interfaces, where they contain infection with pathogenic bacteria and fungi. Beyond this function TH-17 cells have been linked to the pathogenesis of several inflammatory and autoimmune diseases. At present, understanding of Th-17 differentiation is limited to the mouse system and in humans remains still a puzzled issue. Recently it has been proposed IL-1b as a pivotal cytokine in driving Th-17 differentiation. Cryopyrin-associated periodic syndromes (CAPS) are a group of inflammatory diseases associated to mutations of NLRP3 gene encoding the inflammasome component cryopyrin. These mutations determine an exaggerated IL-1b secretion by monocytes upon Toll like receptors (TLRs) stimulation. We have investigated whether the altered IL-1b secretion, secondary to NLPR3 mutations, could affect the IL-23/IL-17 axis in CAPS patients.
IL-17 serum level has been evaluated by ELISA assay. Expression of CCR6 and CD161, two TH-17 specific markers, has been analyzed on CD4+ memory T cells by flow cytometry Frequency of TH-17+ cells has been quantified upon stimulation with staphylococcus entherotoxin B (SEB). Production of IL-1b and IL-23 by monocyte derived dendritic cells (MoDCs), in response to TLRs ligands, has been quantified by ELISA. CAPS patients have been analysed before and after anti-IL1b treatment.
Untreated CAPS patients display significant increased level of serum IL-17 as well as of Th-17+ T cells respect to age matched controls. Both IL-7 serum levels as well as Th-17 frequency decrease after IL-1b treatment. Also production of IL-1b and IL-23 by MoDCs is increased in CAPS patients, and after anti IL-1b treatment production of both cytokines is significantly reduced.
These findings further support a central role of IL-1b in the differentiation of TH 17 in human inflammatory conditions.
To cite this abstract, please use the following information:
Lasiglie, Denise, Traggiai, Elisabetta, Penco, Federica, Federici, Silvia, Accogli, Andrea, Buoncompagni, Antonella, et al; Role of IL-1b in the Development of Human TH17 Cells: Lesson from Patients Carrying NLPR3 Gene Mutations. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :265