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Within tissues, dendritic cells constitute a complex cell population composed of distinct subsets that can exhibit different activation states and functions. How tissue-specific cues orchestrate dendritic cell diversification remains elusive. In the first part of my seminar, I will discuss unpublished results showing that, by reaching distinct sub-tissular niches within the gut, dendritic cells can exist as immature and mature cells, revealing a novel mechanism of dendritic cell functional diversification. In the second part of my seminar, I will present data highlighting the essential role of macrophages in protecting colonic epithelial cells from being poisoned by fungi toxins. I will discuss the implications of these findings on colon inflammation and cancer.