Keystones in lymph node development

Blum, Katrin S.; Pabst, Reinhard

doi:10.1111/j.1469-7580.2006.00650.x

Cited by 47 publications

(35 citation statements)

References 88 publications

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“…Early LyveI ϩ lymph sac cells give rise to both mesenchymal organizer cells and LECs during later LN development. 35 The stromal cell progenitor fate-mapping analysis in embryonic and neonatal LNs, as revealed by the IL-7-Cre transgene, showed that IL-7 promoter activity was almost exclusively restricted to the LEC differentiation pathway. We therefore conclude that IL-7 expression in FRCs, as shown here (and by Link et al 20 ) appears to be a process that is restricted to later stages of LN development (ie, during colonization of LNs by lymphocytes and during adaptive remodeling processes).…”

Section: Discussionmentioning

confidence: 99%

IL-7–producing stromal cells are critical for lymph node remodeling

Onder

Narang

Scandella

et al. 2012

Blood

148

140

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Nonhematopoietic stromal cells of secondary lymphoid organs form important scaffold and fluid transport structures, such as lymph node (LN) trabeculae, lymph vessels, and conduits. Furthermore, through the production of chemokines and cytokines, these cells generate a particular microenvironment that determines lymphocyte positioning and supports lymphocyte homeostasis. IL-7 is an important stromal cell-derived cytokine that has been considered to be derived mainly from T-cell zone fibroblastic reticular cells. We show here that lymphatic endothelial cells ( IntroductionIL-7 is an important cytokine that controls development and activation of different immune cells. 1 The broad expression of this cytokine in primary and secondary lymphoid organs is indicative for its multiple functions. In bone marrow, IL-7 acts on the development of B cells by determining B-cell lineage commitment 2 and regulating immunoglobulin gene arrangement. 3,4 In the thymus, IL-7 serves as a key factor for thymocyte survival and maturation. 5,6 Likewise, IL-7 provides antiapoptotic and proliferative signals to T cells within secondary lymphoid organs and is hence critical for peripheral T-cell homeostasis. 7,8 Furthermore, some intrinsic functions of marginal zone B cells and structural organization of the splenic marginal zone microenvironment depend, at least partially, on IL-7. 9 Besides these effects on T and B lymphocytes, IL-7 can impact on the development of dendritic cells 10 and NK T cells. 11 Hence, because of its pleiotropic functions, IL-7 can be regarded as one of the central regulators of immune cell homeostasis.Besides its direct impact on immune cells, IL-7 acts also on the formation of secondary lymphoid organs. During lymph node (LN) development, for example, IL-7 is produced by VCAM1 ϩ ICAM1 ϩ mesenchymal cells, also known as stromal organizer cells. 12 Stromal cell-derived IL-7 promotes survival of lymphoid tissue inducer (LTi) cells 13 that initiate lymphotoxin-␤ receptor-dependent formation of the LN environment. 14 The importance of IL-7 in LN development and maturation is illustrated by the absence of most peripheral LNs in IL-7R␣-deficient mice. 15,16 Furthermore, overexpression of IL-7 results in the formation of ectopic lymphoid tissues, 17 suggesting that IL-7 critically contributes to the adaptation of lymphoid organ structure during immune reactions.IL-7 production is tightly regulated and detection of both IL-7 protein and mRNA in situ requires highly sensitive detection systems. 18 It has been suggested that IL-7 produced by stromal cells in secondary lymphoid organs is locally consumed by IL-7R␣-expressing cells and that a production-consumption equilibrium regulates lymphocyte homeostasis. 19 Indeed, a recent study suggested that T-cell homeostasis is controlled by T-cell zone fibroblastic reticular cells (FRCs), which exhibited higher IL-7 expression compared with bulk endothelial cell preparations. 20 However, not all IL-7R␣-expressing cells reside in the T-cell zone. For example, IL-7R␣ ϩ ␥␦ T cells ...

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Section: Discussionmentioning

confidence: 99%

IL-7–producing stromal cells are critical for lymph node remodeling

Onder

Narang

Scandella

et al. 2012

Blood

148

140

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“…The development of the lymph node begins at around E10.5 by the budding and sprouting of the lymphendothelial precursor cells from arterial cardiac vein, which later differentiate into lymphatic and blood vascular endothelial cells. The hematopoietic progenitor lymphoid tissue inducer cells arrive at the developing lymph nodes at E12.5-E14.5 (Cupedo et al, 2004;Blum and Pabst, 2006;Drayton et al, 2006). Arf6 mRNA was weakly positive throughout the tissue at E15.5 (Fig.…”

Section: Expression In the Immune Systemsmentioning

confidence: 99%

Tissue‐ and development‐dependent expression of the small GTPase Arf6 in mice

Akiyama

Zhou

Sugimoto

et al. 2010

Developmental Dynamics

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The small GTPase Arf6 is a member of the Arf (ADP-ribosylation factor) family. Although the function of Arf6 has been heavily studied at the cellular level, its physiological function at the whole animal level is largely unknown. In this study, we examined both the tissue distribution and developmental timing of Arf6 expression in wild type mice to obtain valuable information to speculate on the physiological function of Arf6. Western blot analysis using anti-Arf6 antibody revealed that Arf6 was ubiquitously expressed with its developmental timing differing in a tissue-specific manner. These results were supported by Arf6 mRNA in situ hybridization experiments, which showed that Arf6 was highly expressed in the polarized epithelial cells and embryonic mesenchymal cells of most tissues in a temporally dependent manner. Taken in toto, our results suggest that the expression of Arf6 in mouse tissues is precisely regulated in a developmentand tissue-dependent manner. Developmental Dynamics 239:3416-3435,

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“…I n t e s t i n a l l y m p h o i d a g g r e g a t e s ( i L A s ) c a n b e discriminated from PP, which comprises iLF and CP that are closely associated with the epithelial lining in the small and large intestine [30] . CP were defined as tiny aggregates of c-Kit + IL-7R + cells [31] , whereas iLFs are constituted by solitary B follicles that are localized in the anti-mesenteric regions of the intestinal wall, and contain small numbers of mature T lymphocytes, but also c-Kit + and IL-7R + cells [32][33][34] .…”

Section: Dcs In Intestinal Lymphoid Tissuesmentioning

confidence: 99%

Role of mucosal dendritic cells in inflammatory bowel disease

Niess

2008

WJG

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The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents. These local immune responses require a tight control, the outcome of which is in most cases the induction of tolerance. Local T cell immunity is an important compartment of the specific intestinal immune system. T cell reactivity is programmed during the initial stage of its activation by professional presenting cells. Mucosal dendritic cells (DCs) are assumed to play key roles in regulating immune responses in the antigenrich gastrointestinal environment. Mucosal DCs are a heterogeneous population that can either initiate (innate and adaptive) immune responses, or control intestinal inflammation and maintain tolerance. Defects in this regulation are supposed to lead to the two major forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.

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Keystones in lymph node development

Cited by 47 publications

References 88 publications

IL-7–producing stromal cells are critical for lymph node remodeling

IL-7–producing stromal cells are critical for lymph node remodeling

Tissue‐ and development‐dependent expression of the small GTPase Arf6 in mice

Role of mucosal dendritic cells in inflammatory bowel disease

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