The CD27/CD70 pathway negatively regulates visceral adipose tissue-resident Th2 cells and controls metabolic homeostasis.

Adipose tissue homeostasis relies on the interplay between several regulatory lineages, such as type 2 innate lymphoid cells (ILC2s), T helper 2 (Th2) cells, regulatory T cells, eosinophils, and type 2 macrophages. Among them, ILC2s are numerically the dominant source of type 2 cytokines and are considered as major regulators of adiposity. Despite the overlap in immune effector molecules and sensitivity to alarmins (thymic stromal lymphopoietin and interleukin-33) between ILC2s and resident memory Th2 lymphocytes, the role of the adaptive axis of type 2 immunity remains unclear.

Chronic CD27-CD70 costimulation promotes type 1-specific polarization of effector Tregs.

Introduction: Most T lymphocytes, including regulatory T cells, express the CD27 costimulatory receptor in steady state conditions. There is evidence that CD27 engagement on conventional T lymphocytes favors the development of Th1 and cytotoxic responses in mice and humans, but the impact on the regulatory lineage is unknown.

Methods: In this report, we examined the effect of constitutive CD27 engagement on both regulatory and conventional CD4 T cells , in the absence of intentional antigenic stimulation.

PHD2 Constrains Antitumor CD8+ T-cell Activity.

The prolyl hydroxylase domain/hypoxia-inducible factor (PHD/HIF) pathway has been implicated in a wide range of immune and inflammatory processes, including in the oxygen-deprived tumor microenvironment. To examine the effect of HIF stabilization in antitumor immunity, we deleted Phd2 selectively in T lymphocytes using the cre/lox system. We show that the deletion of PHD2 in lymphocytes resulted in enhanced regression of EG7-OVA tumors, in a HIF-1α-dependent manner.

Agonistic anti-CD27 antibody ameliorates EAE by suppressing IL-17 production.

CD27/CD70 costimulation enhances T-cell survival, memory formation and Th1-cell differentiation and effector function. In addition to promoting Th1 responses, CD27 signaling has been shown to exert a negative regulatory role on IL-17 production, resulting in increased sensitivity of CD27 KO mice to EAE. By inducing EAE in full CD27 KO mice, and in a novel, T-cell specific CD27 KO mouse strain (CD4-Cre x CD27 ), we demonstrate herein that CD27 engagement by its natural ligand (CD70) suppresses IL-17 production in a cell autonomous fashion.

PD-1 Is Involved in the Dysregulation of Type 2 Innate Lymphoid Cells in a Murine Model of Obesity.

Recent observations clearly highlight the critical role of type 2 innate lymphoid cells in maintaining the homeostasis of adipose tissues in humans and mice. This cell population promotes beiging and limits adiposity directly and indirectly by sustaining a Th2-prone environment enriched in eosinophils and alternatively activated macrophages. Accordingly, the number and function of type 2 innate lymphoid cells (ILC2s) are strongly impaired in obese individuals.

Apolipoproteins L control cell death triggered by TLR3/TRIF signaling in dendritic cells.

Apolipoproteins L (ApoLs) are Bcl-2-like proteins expressed under inflammatory conditions in myeloid and endothelial cells. We found that Toll-like receptor (TLR) stimuli, particularly the viral mimetic polyinosinic:polycytidylic acid (poly(I:C)), specifically induce ApoLs7/11 subfamilies in murine CD8α(+)  dendritic cells (DCs). This induction requires the TLR3/TRIF (where TRIF is TIR domain containing adapter-inducing interferon β) signaling pathway and is dependent on IFN-β in all ApoLs subfamilies except for ApoL7c.

Cutting Edge: Hypoxia-Inducible Factor 1 Negatively Regulates Th1 Function.

Tissue hypoxia can occur in physiological and pathological conditions. When O2 availability decreases, the transcription factor hypoxia-inducible factor (HIF)-1α is stabilized and regulates cellular adaptation to hypoxia. The objective of this study was to test whether HIF-1α regulates T cell fate and to define the molecular mechanisms of this control.

Thymus-derived regulatory T cells restrain pro-inflammatory Th1 responses by downregulating CD70 on dendritic cells.

The severity and intensity of autoimmune disease in immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) patients and in scurfy mice emphasize the critical role played by thymus-derived regulatory T cells (tTregs) in maintaining peripheral immune tolerance. However, although tTregs are critical to prevent lethal autoimmunity and excessive inflammatory responses, their suppressive mechanism remains elusive. Here, we demonstrate that tTregs selectively inhibit CD27/CD70-dependent Th1 priming, while leaving the IL-12-dependent pathway unaffected.

Intestinal immunopathology is associated with decreased CD73-generated adenosine during lethal infection.

The ectonucleotidases CD39 and CD73 sequentially degrade the extracellular ATP pool and release immunosuppressive adenosine, thereby regulating inflammatory responses. This control is likely to be critical in the gastrointestinal tract where high levels of ATP are released in particular by commensal bacteria. The aim of this study was therefore to evaluate the involvement of the adenosinergic regulation in the intestine of mice in steady-state conditions and on acute infection with Toxoplasma gondii.

Anti-CTLA-4 treatment induces IL-10-producing ICOS+ regulatory T cells displaying IDO-dependent anti-inflammatory properties in a mouse model of colitis.

Background And Aims: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) has been shown to act as a negative regulator of T cell function and has been implicated in the regulation of T helper 1 (Th1)/Th2 development and the function of regulatory T cells. Tests were carried out to determine whether anti-CTLA-4 treatment would alter the polarisation of naive T cells in vivo.

Methods: Mice were treated with anti-CTLA-4 monoclonal antibody (mAb) (UC10-4F10) at the time of immunisation or colonic instillation of trinitrobenzene sulfonic acid (TNBS).