IL-23 Responsive innate-like T cells in spondyloarthritis: the less frequent they are, the more vital they appear

A key role for the IL-23/IL-17 immune axis in spondyloarthritis (SpA) is supported by cumulative evidence from genetic and translational studies and was recently confirmed in clinical trials. Although initially linked to T helper 17 cells, it is now clear that additional unconventional T cell subpopulations respond towards IL-23, including ROR gamma t(+) CD3(+)CD4(-)CD8(-) T cells, TCR gamma delta 17 cells, KIR3DL2(+)CD4(+) T cells and iNKT17 cells. Although these innate-like T cells are present only at low frequencies and often with a specific tissue distribution, it is proposed that they could play a vital function in the development or progression of SpA-related pathology. In this review, we highlight the emerging knowledge on these specialized IL-23 responsive T cells with regard to their relevance in SpA. Finally, we will discuss these findings in light of novel drugs targeting the IL-23/IL-17 axis, currently being tested in SpA patients

Guidelines for the use of flow cytometry and cell sorting in immunological studies

International audienceThe classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127(-) and CD127(+) early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127(-) and CD127(+) ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials. Whereas CD127(-) ELPs comprised precursors of T cells, marginal zone B cells, and natural killer (NK) and innate lymphoid cells (ILCs), CD127(+) ELPs supported production of all NK cell, ILC, and B cell populations but lacked T potential. On the basis of these results, we propose a "two-family" model of human lymphoid development that differs from the prevailing model of hematopoiesis