Summary Interleukin‐17 (IL‐17) has emerged as a central player in the mammalian immune system. Although this cytokine exerts a host‐defensive role in many infectious diseases, it promotes inflammatory pathology in autoimmunity and other settings. A myriad of studies have focused on how IL‐17‐producing cells are generated. However, the means by which IL‐17 achieves its effects, either for the benefit or the detriment of the host, are due in large part to the induction of new gene expression. Whereas many IL‐17 target genes are common to different disease states, in some cases the effects of IL‐17 differ depending on the target cell, infectious site or pathogen. Gene products induced by IL‐17 include cytokines (IL‐6, granulocyte‐colony‐stimulating factor, tumour necrosis factor‐α), chemokines (CXCL1, CXCL2, CCL20, among many others), inflammatory effectors (acute‐phase protesins, complement) and antimicrobial proteins (defensins, mucins). Different cell types appear to respond differently to IL‐17 in terms of target gene expression, with notable differences seen in mesenchymal and epithelial cells compared with cells of haematopoietic origin. Here, we summarize the major IL‐17 target genes that mediate this cytokine’s activities in both autoimmune and chronic diseases as well as during various types of infections.

Summary The importance of T helper type 1(Th1) immunity in host resistance to the intracellular bacterium Francisella tularensis is well established. However, the relative roles of Interleukin (IL)-12/Th1 and IL-23/T helper type 17(Th17) responses in immunity to F.tularensis have not been studied. The IL-23/Th17 pathway is critical for protective immunity against extracellular bacterial infections. In contrast, the IL-23/Th17 pathway is dispensable for protection against intracellular pathogens such as Mycobacteria. Our data show that the IL-23/Th17 pathway regulates the IL-12/Th1 pathway and is required for protective immunity against F.tularensis Live Vaccine Strain (LVS). We show that IL-17, but not IL-17F or IL-22 induces IL-12 production in dendritic cells and mediates Th1 responses. Furthermore, we show that IL-17 also induces IL-12 and IFNγ production in macrophages and mediates bacterial killing. Together, these findings illustrate a novel biological function for IL-17 in regulating IL-12/Th1 immunity and host responses to an intracellular pathogen.

Takeuchi et al. demonstrate that CRTAM identifies CD4 T cells with cytotoxic function, and present new insights into CD4+CTL development.

Ror2 receptor tyrosine kinase plays crucial roles in developmental morphogenesis and tissue-/organo-genesis. In the developing brain, Ror2 is expressed in neural stem/progenitor cells (NPCs) and involved in the regulation of their stemness. However, it remains largely unknown about its role in the adult brain. In this study, we show that Ror2 is up-regulated in reactive astrocytes in the neocortices within 3 days following stab-wound injury. Intriguingly, Ror2-expressing astrocytes were detected primarily at the area surrounding the injury site, where astrocytes express Nestin, a marker of NPCs, and proliferate in response to injury. Furthermore, we show by using astrocyte-specific Ror2 knockout (KO) mice that a loss of Ror2 in astrocytes attenuates injury-induced proliferation of reactive astrocytes. It was also found that basic fibroblast growth factor (bFGF) is strongly up-regulated at 1 day post injury in the neocortices, and that stimulation of cultured quiescent astrocytes with bFGF restarts their cell cycle and induces expression of Ror2 during the G1 phase predominantly in proliferating cells. By using this culture method, we further show that the proportions of Ror2-expressing astrocytes increase following treatment with the histone deacetylases inhibitors including valproic acid, and that bFGF stimulation increases the levels of Ror2 expression within the respective cells. Moreover, we show that bFGF-induced cell cycle progression into S phase is inhibited or promoted in astrocytes from Ror2 KO mice or NPCs stably expressing Ror2-GFP, respectively. Collectively, these findings indicate that Ror2 plays a critical role in regulating the cell cycle progression of reactive astrocytes following brain injury, GLIA 2016. GLIA 2017;65:182-197.