Organogenesis of lymphoid tissues

Mebius, Reina E.

doi:10.1038/nri1054

Cited by 640 publications

(553 citation statements)

References 87 publications

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“…Analysis of the role of NF-kB in lymphoid organogenesis in knockouts has been complicated by the necessity of interfering with the TNF response to rescue the lethality associated with NF-kB deficiency. The initial events of lymphoid organogenesis involve the association of lymphotoxin (LT)a 1 b 2 -expressing hematopoietic cells and vascular cell adhesion molecule-1 (VCAM1)-expressing stromal cells (for a review see Mebius, 2003). This interaction initiates a positive feedbacksignaling loop in which NF-kB plays a prominent role ( Figure 3).…”

Section: Secondary Lymphoid Organsmentioning

confidence: 99%

“…Mice with a point mutation in nik (aly/aly mice) lack multiple secondary lymphoid organs (Miyawaki et al, 1994;Koike et al, 1996;Shinkura et al, 1999) and share several phenotypic similarities with lymphotoxin and IKKa single knockout animals (Mebius, 2003;Bonizzi and Karin, 2004). p52/RelB, which is activated downstream of NIK and IKKa, is thought to be the primary transcriptional mediator of several key organogenic factors including CXCL12, CXCL13, CCL19, CCL21 and MadCAM-1 (Yilmaz et al, 2003).…”

Section: Secondary Lymphoid Organsmentioning

confidence: 99%

“…Although the role of NF-kB in cancer biology is becoming progressively better established, historically much of our current knowledge of NF-kB resulted from efforts directed at understanding the regulation and function of the immune response. In keeping with the critical role played by NF-kB in different areas of immunology, numerous excellent reviews have been published covering the role of NF-kB in Toll-like receptor (TLR) and antigen receptor (AgR) signaling, lymphoid organogenesis and hematopoiesis (Mebius, 2003;Bonizzi and Karin, 2004;Hayden and Ghosh, 2004;Lin and Wang, 2004;Siebenlist et al, 2005;Akira et al, 2006). This review will, therefore, attempt to provide a more comprehensive, if less detailed, review of the diverse functions of NF-kB in immunology, with the goal of illuminating how it is that so much in immunology seems to revolve around this family of transcription factors.…”

Section: Introductionmentioning

confidence: 99%

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NF-κB and the immune response

2006

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Section: Secondary Lymphoid Organsmentioning

confidence: 99%

Section: Secondary Lymphoid Organsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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NF-κB and the immune response

2006

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“…This heterotrimer binds exclusively to another receptor, the LT␤ receptor (LT␤R), which is expressed on nonlymphoid cells (4). Over the past years, a wealth of data has indicated an indispensable role for the LT␣␤-LT␤R interaction in secondary lymphoid organ structure development and function (5,6). In addition, some studies have shown a functional impairment in generating secondary antibody responses to certain antigens in LT-deficient mice, although normal numbers of T and B cells are found (7,8).…”

mentioning

confidence: 99%

A unique lymphotoxin αβ-dependent pathway regulates thymic emigration of Vα14 invariant natural killer T cells

Franki

Beneden²,

Dewint³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Natural killer (NK) T cells using an invariant V␣14 (V␣14i) T cell receptor rearrangement form a distinct immunoregulatory T cell lineage. Several studies indicated that a NK1.1 ؊ V␣14i NKT precursor cell differentiates and expands within the thymus before export to the peripheral tissues occurs. However, little is known about the signals that cause the emigration of V␣14i NKT cells from the thymus to the periphery. Here we show that signaling of lymphotoxin (LT) ␣␤ through the LT␤ receptor (LT␤R) is indispensable for regulating peripheral but not thymic V␣14i NKT cell numbers. Homing to and homeostatic proliferation of thymic V␣14i NKT cells in peripheral organs, however, was not dependent on LT␤R. Instead, our data indicate that a LT␤R-expressing thymic stromal cell regulates the thymic emigration of V␣14i NKT cells but not conventional T cell receptor ␣␤ cells.ymphotoxin (LT) ␣ and ␤ are members of the TNF family that form biologically active homotrimers or heterotrimers. LT␣ can be secreted as a homotrimer that can bind with equal affinity to either TNF receptor 1 or 2 (1). LT␣ can also be membrane-bound by association with LT␤ to form LT␣␤ (2, 3). This heterotrimer binds exclusively to another receptor, the LT␤ receptor (LT␤R), which is expressed on nonlymphoid cells (4). Over the past years, a wealth of data has indicated an indispensable role for the LT␣␤-LT␤R interaction in secondary lymphoid organ structure development and function (5, 6). In addition, some studies have shown a functional impairment in generating secondary antibody responses to certain antigens in LT-deficient mice, although normal numbers of T and B cells are found (7,8).Natural killer (NK) T cells recognize glycolipid antigens (9, 10), and they form a unique lymphocyte subset with important immunoregulatory properties (11). They coexpress NK receptors and intermediate levels of T cell receptor (TCR) ␣␤ and have a phenotype reminiscent of activated T cells. Several distinct subsets of NKT cells have been described (12). In mice the most abundant NKT cell subpopulation is characterized by an invariant TCR␣ rearrangement, V␣14-J␣18, and is reactive with CD1d, a nonclassical class I antigen-presenting molecule (13,14). We will hereafter refer to these cells as V␣14 invariant (V␣14i) NKT cells. Upon recognition of the synthetic glycolipid ␣-galactosylceramide (␣-GalCer), which is presented by CD1d (10), TCR stimulation results in the rapid production of proinflammatory cytokines that influence other immune cells, including NK cells, dendritic cells, and B and T cells (11).There is evidence that V␣14i NKT cells form a separate T cell lineage because they are selected in the thymus by a hematopoietic cell type, which contrasts with the selection of conventional T cells by thymic epithelial cells (15)(16)(17)(18). With the availability of ␣-GalCer-loaded CD1d tetramers (19), important new information has been obtained about V␣14i NKT cell ontogeny, showing that NK1.1 receptor expression is modulated during development, meaning that not all V␣...

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“…Such cells, if autoreactive, could therefore be primed directly at the site of inflammation [91]. After activation, naïve T cells upregulate membrane lymphotoxin (primarily LTα 1 β 2 ) [90, 92, 93], which is an important factor in the formation of organized lymphoid tissue [94]. LT may contribute to the development of HEV and organized lymphoid tissue by further augmenting CCL21 expression and other lymphocyte traffic molecules, thus establishing a positive feedback loop [94, 95, 96].…”

Section: Naïve T Cell Recirculation and Interstitial Migrationmentioning

confidence: 99%

Visualizing T Cell Migration in vivo

Iparraguirre

Weninger²

2003

Int Arch Allergy Immunol

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Ever since the realization that T lymphocytes are key players in the defense against pathogens and tumors, a major aim of immunologists has been to understand the relationship between the functional and migratory properties of antigen-specific T cells. The current paradigm proposes that T cells follow organ-specific trafficking pathways to exit from blood into the extravascular compartment. T cell homing is regulated at the level of adhesion molecules and chemokine receptors, whose expression is linked tightly to the differentiation state of the cell. Naïve T lymphocytes follow relatively uniform recirculation routes through secondary lymphoid organs, the molecular cues of which are fairly well understood. As effector and memory T cells must be capable of reaching virtually any site in the body, their migratory behavior is considerably more heterogeneous. During the past few years, innovative approaches for tracking T cells in vivo have emerged. Here, we review recent technical developments in experimental methods for the visualization of T cells both at the population and single cell level in vivo, and discuss what these methods have taught us about T cell trafficking.

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Organogenesis of lymphoid tissues

Cited by 640 publications

References 87 publications

NF-κB and the immune response

NF-κB and the immune response

A unique lymphotoxin αβ-dependent pathway regulates thymic emigration of Vα14 invariant natural killer T cells

Visualizing T Cell Migration in vivo

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