Abstract: The invention provides chimeric antigen receptors (CARs), nucleic acid sequences encoding a CAR, vectors comprising a nucleic acid sequence encoding a CAR, cells expressing a CAR, pharmaceutical compositions comprising a cell expressing a CAR, wherein the CAR binds to a target molecule expressed on disease-associated macrophages or over- or aberrantly-expressed in fibrosis. The invention further provides vectors encoding a CAR and a fibrotic disease-modulatory molecule (FDMM), and cells expressing both a CAR and an FDMM. The invention also provides methods of treating a subject using a CAR, a nucleic acid sequence, a vector or vectors, or a CAR-expressing cell, a cell expressing both a CAR and an FDMM, or a pharmaceutical composition, and to methods of generating a CAR-expressing cell or a cell expressing both a CAR and an FDMM.

Abstract: The invention relates to a CD161 ligand known as Proliferation-Induced Lymphocyte-Associated Receptor (PILAR), which is crucial for a robust expansion of human lymphocytes. PILAR is markedly up-regulated on both CD4 and CD8 T cells upon TCR engagement and increases the expression of anti-apoptotic genes and glucose transporters through CD161, which globally results in a dramatic enhancement of T cell proliferation. Agents which stimulate or block this activity are also provided as are methods for manipulating PILAR signaling in the treatment of disease.

Abstract: The invention relates to a CD161 ligand known as Proliferation-Induced Lymphocyte-Associated Receptor (PILAR), which is crucial for a robust expansion of human lymphocytes. PILAR is markedly up-regulated on both CD4 and CD8 T cells upon TCR engagement and increases the expression of anti-apoptotic genes and glucose transporters through CD161, which globally results in a dramatic enhancement of T cell proliferation. Agents which stimulate or block this activity are also provided as are methods for manipulating PILAR signaling in the treatment of disease.