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Education of our intestinal immune system early in life strongly influences adult health. This education strongly relies on series of events that must occur in well‐defined time windows. From initial colonization by maternal‐derived microbiota during delivery to dietary changes from mother's milk to solid foods at weaning, these early‐life events have indeed long‐standing consequences on our immunity, facilitating tolerance to environmental exposures or, on the contrary, increasing the risk of developing noncommunicable diseases such as allergies, asthma, obesity, and inflammatory bowel diseases. In this review, we provide an outline of the recent advances in our understanding of these events and how they are mechanistically related to intestinal immunity development and education. First, we review the susceptibility of neonates to infections and inflammatory diseases, related to their immune system and microbiota changes. Then, we highlight the maternal factors involved in protection and education of the mucosal immune system of the offspring, the role of the microbiota, and the nature of neonatal immune system until weaning. We also present how the development of some immune responses is intertwined in temporal and spatial windows of opportunity. Finally, we discuss pending questions regarding the neonate particular immune status and the activation of the intestinal immune system at weaning. [ABSTRACT FROM AUTHOR]

Mucosal immune responses in the inductive lymphoid tissues of the intestine begin with uptake of particulate antigens, including components of the gut microbiota by specialized antigen sampling M cells. M cells represent a distinct lineage of enterocytes that arise from crypt stem cells in response to the cytokine receptor of NF‐κB ligand (RANKL). Full differentiation of M cells requires the transcription factor Spi‐B to yield mature M cells that express multiple receptors for bacteria including glycoprotein 2. M cell differentiation can be recapitulated in vitro using three‐dimensional enteroid cultures of primary intestinal stem cells supplemented with RANKL. This article summarizes the current knowledge about the genesis of intestinal M cells and highlights some of the remaining unanswered questions about this enigmatic cell type. M cells are specialized intestinal epithelial cells that are essential for uptake of intestinal luminal antigens for gut‐associated lymphoid tissue to evoke antigen‐specific intestinal immune responses. In this decade, various molecules preferentially expressed by M cells have been identified and investigated extensively, especially antigen‐uptake receptors and transcription factors directing differentiation. However, the molecular basis of apical‐to‐basal transcytosis remains poorly understood. Herein, the history of M‐cell biology is presented, including the most salient discoveries to date and the still unsolved enigmas. [ABSTRACT FROM AUTHOR]