Vijay Kumar Kuchroo

In the Kuchroo laboratory, our overarching goal is elucidating the mechanisms that regulate immune functions in health, aging and different disease contexts. We focus on the functions of different CD4+ T helper subsets, and the role of costimulatory pathways in the activation and differentiation of T cells. Aside from Th1/Th2 cells, it is now appreciated that other T cell subsets – including IL-17-secreting Th17 cells, IL-9/IL-10-secreting Th9 cells, and IL-10-secreting Tr1 cells – have a major influence on tissue inflammation and autoimmunity (Schnell et al., Cell 2021). Our laboratory was among the first to characterize and identify factors required to induce the differentiation Th17 cells, Th9 cells and Tr1 cells from naïve T cells. Specifically, we demonstrated that a combination of pro- and anti-inflammatory cytokines, IL-6 and TGF-, induce Th17 cell differentiation (Bettelli et al., Nature 2006), and that Th17 cells produce IL-21, which further amplifies the generation of Th17 cells. We also identified IL-27 as a major inducer of Tr1 cells and showed that IL-27-induced Tr1 cells suppress autoimmune inflammation. In ongoing work, we are investigating the molecular mechanisms that drive the development of Th17 and Tr1 cells by expression profiling and CRISPR-Cas9 screening of T cell differentiation (Hou et al., Nature 2024) in the context of infection, autoimmunity and cancer, studies which have revealed key steps in the differentiation of T cell subsets.
We have a long-standing interest in immune checkpoint pathways. The identification of a negative regulator of T cell function, Tim (T cell Immunoglobulin and Mucin)-3 (Monney et al., Nature 2002), in our lab led to the subsequent discovery of the TIM family of molecules, including Tim-1, Tim-2, Tim-3 and Tim-4. Such immune checkpoint receptors ensure contraction of antigen-specific lymphocytes during an immune response. Defects in these immune regulators have been implicated in the pathogenesis of multiple autoimmune diseases. Conversely, we demonstrated that Tim-3 is expressed on exhausted T cells in chronic viral infections and constrains the function of tumor infiltrating lymphocytes that exhibit an exhausted phenotype. We discovered that Tim-3 expression is not limited to T cells and are currently studying how Tim-3 expressed on dendritic cells regulate the generation of stem-like T cells and T cell exhaustion in cancer and chronic viral infections. Motivated by recent human genomic studies that link Tim-3 with Alzheimer’s disease, we are exploring the role of Tim-3 and other immune checkpoint molecules in microglial cells, the immune cells of the brain (Kimura et al., Nature 2025). Our research also revealed that another member of the TIM family, Tim-1, acts as a checkpoint molecule in B cells, where it regulates anti-tumor immunity (Bod et al., Nature 2023).
More recently, our research has expanded to neuroimmune interactions that regulate immune responses. We were the first to describe the immuno-modulatory role of neuropeptides, by demonstrating that Neuromeudin U (NMU) (Wallrapp et al., Nature 2017) promotes type II inflammation. We revealed that immune cell-derived type II cytokines, like IL-4 and IL-13, reciprocally induces the production of neuropeptides like NMU during type II inflammation at barrier sites (Barilla et al., Science 2025).