Article

Opening the crypt: current facts and hypotheses on the function of cryptopatches

CNRS URA1961, Paris 75724, France. <>
Trends in Immunology (Impact Factor: 10.4). 12/2009; 31(2):50-5. DOI: 10.1016/j.it.2009.11.004
Source: PubMed

ABSTRACT

Cryptopatches, small aggregates of lymphoid cells found in the intestinal lamina propria, have been assigned many functions specific to gut immunity. Populated with seemingly immature lymphoid cells and dendritic cells, it has been suggested that cryptopatches maturate intraepithelial lymphocytes, Th17 cells, IL-22-producing NKp46(+) cells, and lymphoid tissues in response to the gut microbiota. Some of these issues, however, remain hotly debated. Therefore, cryptopatches are coming to the forefront of gut immunology and warrant a comprehensive discussion of their role in the development of the immune system.

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    • "To date attention has focussed on the capacity of ILCs in tissue to produce immune modulatory cytokines with little emphasis on how ILC positioning within a tissue may impact on functional outcomes. Under non-inflammatory conditions, ILCs are found within lymphoid structures in the colon (Eberl and Sawa, 2010), and in Rag-deficient hosts these structures are limited to cryptopatches as there are no B cells to form ILFs. Under homeostatic conditions ILCs primarily reside within lymphoid aggregate cryptopatch (CP) structures (Figure 4A) and are found only rarely within the non-inflamed lamina propria . "
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    ABSTRACT: Innate lymphoid cells (ILCs) contribute to host defence and tissue repair but can induce immunopathology. Recent work has revealed tissue-specific roles for ILCs; however, the question of how a small population has large effects on immune homeostasis remains unclear. We identify two mechanisms that ILC3s utilise to exert their effects within intestinal tissue. ILC-driven colitis depends on production of granulocyte macrophage-colony stimulating factor (GM-CSF), which recruits and maintains intestinal inflammatory monocytes. ILCs present in the intestine also enter and exit cryptopatches in a highly dynamic process. During colitis, ILC3s mobilize from cryptopatches, a process that can be inhibited by blocking GM-CSF, and mobilization precedes inflammatory foci elsewhere in the tissue. Together these data identify the IL-23R/GM-CSF axis within ILC3 as a key control point in the accumulation of innate effector cells in the intestine and in the spatio-temporal dynamics of ILCs in the intestinal inflammatory response.
    Full-text · Article · Jan 2016 · eLife Sciences
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    • "The number of ILF in the gut is invariant, but those present are morphologically dynamic, and thus have been collectively termed solitary isolated lymphoid tissue (SILT) [16]. SILT initially derive from cryptopatches, precursor structures located at the base of the crypts that are formed independently of bacterial colonization [16], [17]. Immature ILF are induced by initial acquisition of enteric microbiota and consist of few B220+ B cells framed by CD11c+ dendritic cells (DC), and few CD3+ T cells. "
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    ABSTRACT: 18β-glycyrrhetinic acid (GRA) is a pharmacologically active component of licorice root with documented immunomodulatory properties. We reported that GRA administered orally to mice induces B cell recruitment to isolated lymphoid follicles (ILF) in the small intestine and shortens the duration of rotavirus antigen shedding. ILF are dynamic lymphoid tissues in the gut acquired post-natally upon colonization with commensal bacteria and mature through B cell recruitment to the follicles, resulting in up-regulation of IgA synthesis in response to changes in the composition of microbiota. In this study, we investigated potential mechanisms by which GRA induces ILF maturation in the ileum and the colon using mice depleted of enteric bacteria and a select group of mice genetically deficient in pattern recognition receptors. The data show GRA was unable to induce ILF maturation in ileums of mice devoid of commensal bacteria, MyD88-/- or NOD2-/- mice, but differentially induced ILF in colons. Increased expression of chemokine and chemokine receptor genes that modulate B and T cell recruitment to the mucosa were in part dependent on NOD2, TLR, and signaling adaptor protein MyD88. Together the results suggest GRA induces ILF through cooperative signals provided by bacterial ligands under normal conditions to induce B cell recruitment to ILF to the gut, but that the relative contribution of these signals differ between ileum and colon.
    Full-text · Article · Jul 2014 · PLoS ONE
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    • "The lymphoid system possesses highly specialized peripheral organs formed at strategic anatomical sites that constitute threedimensional platforms ensuring efficient immune-surveillance, rapid immune responses and maintenance of protective immunity . Secondary lymphoid organs (SLO), such as lymph nodes (LN) and Peyer's patches (PP), develop during the embryonic life, but can also assemble after birth as it occurs with enteric cryptopatches and isolated lymphoid follicles (Randall et al., 2008; Eberl and Sawa, 2010; van de Pavert and Mebius, 2010; Neyt et al., 2012). "
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    ABSTRACT: The lymphoid system is equipped with a network of specialized platforms located at strategic sites, which grant strict immune-surveillance and efficient immune responses. The development of these peripheral secondary lymphoid organs (SLO) occurs mainly in utero, while tertiary lymphoid structures can form in adulthood generally in response to persistent infection and inflammation. Regardless of the lymphoid tissue and intrinsic cellular and molecular differences, it is now well established that the recruitment of fully functional lymphoid tissue inducer (LTi) cells to presumptive lymphoid organ sites, and their consequent close and reciprocal interaction with resident stroma cells, are central to SLO formation. In contrast, the nature of events that initially prime resident sessile stroma cells to recruit and retain LTi cells remains poorly understood. Recently, new findings revealed early phases of SLO development putting emphasis on mesenchymal and lymphoid tissue initiator cells. Herein we discuss the main tenets of enteric lymphoid organs genesis and focus in the most recent findings that open new perspectives to the understanding of the early phases of lymphoid morphogenesis.
    Full-text · Article · Jul 2012 · Frontiers in Immunology
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