"Immunological memory provides immunity against recurrent pathogens, but also can induce and regulate immunopathology. In chronic immune-mediated diseases, a ""pathogenic"" immunological memory probably is the essential driver of inflammation, refractory to physiological regulation and state-of-the-art therapeutic immunosuppression, and thus a challenge for the development of novel, curative therapeutic strategies. Despite its relevance, immunological memory is poorly understood. We recently discovered memory plasma cells and professional memory T helper cells, and their organisation by bone marrow stroma and the stroma of inflamed tissues. We have identified genes and regulating function and persistence of memory and effector cells in the resting state and in chronic immune reactions. Based on these intriguing, paradigm-breaking initial results, I propose to develop and lead a research program addressing the organisation and role of immunological memory in protective immunity and in immune-mediated diseases, on the systemic, cellular and molecular level. In particular, I propose to (1) analyse the homing of plasmablasts and T helper memory cell precursors to dedicated survival niches of the bone marrow or inflamed tissues, (2) identify the niches of CD8 memory cells and memory B cells, (3) analyse the cellular and molecular composition of memory niches, (4) decipher the molecular communication between stromal cells and immune memory cells, (5) analyse how memory/effector T helper cells are reactivated, (6) define the role of memory-phenotype T cells in the periphery, (7) analyse the role of twist1 and hop for persistence and function of pathogenic Th memory/effector cells, and (8) develop strategies to selectively delete pathogenic immune memory cells."
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