In this report, we have demonstrated that IL-15 plays an important role in supporting FDC proliferation and in the production of certain chemokines by FDCs. These findings suggest that IL-15 is one of the key factors in the production of protective antibodies by stimulating rapid GC formation, offering a potential target for immune modulation. This study was initiated at the Laboratory of Cellular Immunology (Ochsner Clinic Foundation, New Orleans, LA) and completed at the Asan Institute for Life Science, Seoul. The reagents IL-15 and CD40L were the generous gift of Dr Richard Armitage (Amgen, Seattle, WA). The study was supported by a grant W06-408 from the Asan Institute for
Life Science, Seoul, and by a National Research Foundation grant from the Korean government A (R13-2008-023-01003). Selleck Ibrutinib None of the authors have any potencial financial conflict of interest related to this work. “
“Invariant natural killer T (iNKT) cells are a distinct lineage of innate-like T lymphocytes and converging studies in mouse models have demonstrated the protective role of iNKT cells in the development of type 1 diabetes. Recently, a new subset of iNKT cells, producing high levels of the pro-inflammatory cytokine IL-17, has check details been identified
(iNKT17 cells). Since this cytokine has been implicated in several autoimmune diseases, we have analyzed iNKT17 cell frequency, absolute number and phenotypes in the pancreas and lymphoid organs in non-obese diabetic (NOD) mice. The role of iNKT17 cells in the development of diabetes was investigated using transfer experiments. NOD mice exhibit a higher frequency and absolute number of iNKT17 cells in the lymphoid organs as compared with C57BL/6 mice. iNKT17 cells infiltrate the pancreas of NOD mice where they express IL-17 mRNA. Contrary
to the protective role of CD4+ iNKT cells, the CD4− iNKT cell population, which contains iNKT17 cells, enhances the incidence of diabetes. Treatment with a blocking anti-IL-17 antibody prevents the exacerbation of the disease. This study reveals that different iNKT cell subsets play distinct roles in the regulation of type 1 diabetes and iNKT17 cells, which are abundant in NOD mice, exacerbate Org 27569 diabetes development. Invariant natural killer T (iNKT) cells represent a distinct lineage of T cells that co-express a highly conserved αβ T-cell receptor TCR along with typical surface receptors for natural killer cells. The invariant TCRα chain of iNKT cells is encoded by Vα24-Jα18 gene-segments in humans and Vα14-Jα18 gene-segments in mice. The TCRβ chain is also strongly biased, encoded by Vβ11 gene-segment in humans and Vβ8.2, Vβ7 and Vβ2 gene-segments in mice. These lymphocytes recognize both self and microbial glycolipid antigens presented by the non-classical class I molecule CD1d.