Abstract: The present invention relates to chimeric receptors (e.g. CARs including both single chain and multichain CARs) that bind to TREM2 ligands and their use in therapy. In particular, the invention provides a chimeric receptor comprising: (a) an exodomain comprising the ligand binding domain of TREM2 or a functional variant thereof, optionally wherein said exodomain is resistant to cleavage by a sheddase; (b) a transmembrane domain; and (c) an endodomain comprising an intracellular signalling domain.

Abstract: The present invention provides an engineered regulatory T cell (Treg) comprising a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen recognition domain which specifically binds to asialoglycoprotein receptor (ASGR). The present invention also provides a method of promoting liver tissue repair and/or regeneration in a subject which comprises the step of administering to the subject an engineered Treg comprising a CAR or a pharmaceutical composition comprising the engineered Treg, wherein the CAR comprises a liver-specific antigen recognition domain.

Abstract: The present invention provides an engineered regulatory T cell (Treg) comprising a chimeric antigen receptor (CAR) for use in induction of tolerance to a transplant; treating and/or preventing graft-versus-host disease (GvHD), an autoimmune or allergic disease; to promote tissue repair and/or tissue regeneration; or to ameliorate chronic inflammation secondary to metabolic disorders; wherein the CAR comprises an endodomain which comprises a STAT association motif and a JAK1- and/or a JAK2-binding motif.

Abstract: The invention relates to isolated polypeptides and nucleic acids encoding polypeptides which comprise a tim-3 IgV domain and a tim-3 intracellular domain, wherein the polypeptides do not comprise a tim-3 mucin domain or a tim-3 transmembrane domain. In addition, the invention relates to methods of modulating immune responses in a subject, comprising administering to the subject a therapeutically effective amount of an agent that modulates tim-3 activity. Immune responses include, but are not limited to, immune tolerance, transplantation tolerance, Th1 responses and Th2 responses.

Abstract: The invention relates to isolated polypeptides and nucleic acids encoding polypeptides which comprise a tim-3 IgV domain and a tim-3 intracellular domain, wherein the polypeptides do not comprise a tim-3 mucin domain or a tim-3 transmembrane domain. In addition, the invention relates to methods of modulating immune responses in a subject, comprising administering to the subject a therapeutically effective amount of an agent that modulates tim-3 activity. Immune responses include, but are not limited to, immune tolerance, transplantation tolerance, Th1 responses and Th2 responses.

Abstract: The invention refers to a method and kit for the in vitro diagnosis and/or prognosis of the tolerant state of a patient to be submitted to liver transplantation, which comprises assessing the level of systemic and/or intra-hepatic iron stores in a biological sample obtained from the patient under investigation, and comparing it either with the level of iron stores of a reference sample, or with a pre-determined threshold.

Abstract: The invention relates to isolated polypeptides and nucleic acids encoding polypeptides which comprise a tim-3 IgV domain and a tim-3 intracellular domain, wherein the polypeptides do not comprise a tim-3 mucin domain or a tim-3 transmembrane domain. In addition, the invention relates to methods of modulating immune responses in a subject, comprising administering to the subject a therapeutically effective amount of an agent that modulates tim-3 activity. Immune responses include, but are not limited to, immune tolerance, transplantation tolerance, Th1 responses and Th2 responses.

Abstract: In vitro diagnosis/prognosis method and kit, for assessment of tolerance in liver transplantation. The present invention refers to the study of peripheral blood transcriptional patterns from 80 liver transplant recipients and 16 non-transplanted healthy individuals employing either oligonucleotide microarrays and/or quantitative real-time PCR to design a clinically applicable molecular test. This has resulted in the discovery and validation of several gene signatures comprising a modest number of genes capable of identifying tolerant and non-tolerant recipients with high accuracy. The marker genes are KLRF1, SLAMF7, NKG7, IL2RB, KLRB1, FANCG, GNPTAB, CLIC3, PSMD14, ALG8, CX3CR1, RGS 3. Multiple peripheral blood lymphocyte subsets contribute to the tolerance-associated transcriptional patterns with NK and ?delta T cells exerting a predominant influence.

Abstract: The long-term survival of transplanted grafts critically depends on the life-long administration of immunosuppressive drugs to prevent graft rejection. These drugs are very effective at preventing graft rejection, but they are also associated with severe side effects. Inventors have selected a set of genes whose expression characterizes the tolerant state in liver transplantation in humans. Based on the expression level profile of this set of genes, inventors provide a non-invasive method to assess diagnosis and/or prognosis of the tolerant state in liver transplantation in humans, and kits to perform it. These kits are simpler and cheaper than others based on a great number of genes, such as commercial microarrays with thousands of probes.

Abstract: The invention relates to isolated polypeptides and nucleic acids encoding polypeptides which comprise a tim-3 IgV domain and a tim-3 intracellular domain, wherein the polypeptides do not comprise a tim-3 mucin domain or a tim-3 transmembrane domain. In addition, the invention relates to methods of modulating immune responses in a subject, comprising administering to the subject a therapeutically effective amount of an agent that modulates tim-3 activity. Immune responses include, but are not limited to, immune tolerance, transplantation tolerance, Th1 responses and Th2 responses.