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We engineered CD8+ T cells with two orthogonal cytokines for adoptive cell transfer into mice with solid tumors. These cells acquired a novel synthetic effector state that fully deviated from TOX+ canonical exhaustion and displayed improved anti-tumor effector functions.
Many immune cell subsets move in an amoeboid fashion and do not require strong adhesive interactions with their surrounding when moving through interstitial tissue spaces. In stark contrast, we show that mast cells critically depend on integrin-mediated adhesion and interactions with the extracellular matrix to enable slow migration and site-specific positioning in tissues.
Regulatory T (Treg) cells respond to interferon-γ (IFNγ) during viral infection and polarize to a T helper (TH)1-like state. Such Treg cells possess effector functions, such as the production of IFNγ, yet remain stable and potently limit virus-specific effector T cell function, CD8+ T cell proliferation and the formation of central memory T cells.
We show a crucial protective function for T follicular helper (TFH)-like cells localized within granuloma-associated lymphoid tissue for Mycobacterium tuberculosis control in mouse models of tuberculosis. Antigen-specific B cells contribute to this strategic localization and the maturation of cytokine-producing TFH-like cells.
When an interstitial macrophage niche is empty, classical monocytes can proliferate locally in a manner that is restricted by the transcription factor MAFB, before undergoing differentiation into distinct macrophage subsets. These findings reveal a new function of monocytes and highlight the complex regulation of proliferation and differentiation during macrophage development.
Homozygous expression of MHC-II alleles that confer susceptibility to type 1 diabetes limits the efficiency of thymic negative selection and allows for CXCR6+ pathogenic clones to orchestrate the disease process. Expression of a second MHC-II allele decreases β-islet CD4+ T cell affinity, and limits CD8 cross-priming and diabetes risk without presenting the cognate MHC-II islet self-antigen.
The cholesterol metabolite receptor GPR183 regulates the secretion of IgA by intestinal plasma cells. This process requires epithelial cell sensing of commensal bacteria and the uptake of dietary cholesterol to generate the GPR183 ligand 7α,25-hydroxycholesterol. Upon GPR183 activation, IgA+ plasma cells remain at the center of intestinal villi and reduce their antibody secretion.
Intrathymic dendritic cell (DC)-biased precursors act as hematopoietic stromal cells that support the generation of human T cell progenitors from hematopoietic progenitor cells, via crosstalk with immature thymocytes that express TNF receptor 2. This function of DC precursors can be exploited to generate T cell precursors and competent T cells for cell therapy.
Exhausted effector T cells accumulate in tumors and are the intended targets of cancer immunotherapy. New data suggest that upon infiltration and subsequent exhaustion in the tumor microenvironment, these T cells can take on an immunosuppressive function — and work against the immune response to cancer.
Sterol regulatory element-binding protein (SREBP) signaling regulates cellular lipid homeostasis. We discovered that SREBP signaling in B cells is crucial for antibody responses and the generation of germinal centers and B cell memory compartments in response to vaccination. These results provide mechanistic insights that couple sterol metabolism to the quality and longevity of humoral immunity.
