Critical role for β7 integrins in formation of the gut-associated lymphoid tissue

Wagner, Norbert; Löhler, Jürgen; Kunkel, Eric J.; Ley, Klaus; Leung, Euphemia; Krissansen, G. W.; Rajewsky, Klaus; Müller, Werner

doi:10.1038/382366a0

Cited by 532 publications

(430 citation statements)

References 28 publications

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“…Alternatively, the rapid pace of fetal and placental development in the mouse, with most of the immunologically critical events occurring within the first 2 weeks, makes it possible to carry out "poorman's knockout experiments" using mAb to inhibit the contribution of target adhesion pathways or to deplete antigenetically defined leukocyte subsets. In addition, we studied selected gene-deficient models (b7-integrin -/-and P-selectin -/-mice) [16,17] by immunohistological analysis of the maternal/fetal unit in midterm pregnancies in genetically homozygous females.…”

Section: Discussionmentioning

confidence: 99%

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Functional involvement of P‐selectin and MAdCAM‐1 in the recruitment of α4β7‐integrin‐expressing monocyte‐like cells to the pregnant mouse uterus

et al. 2004

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Leukocyte recruitment to the pregnant mouse uterus has been suggested to be associated with highly regulated expression of distinct patterns of vascular adhesion receptors. One of the most striking observations is the combined expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and P-selectin by maternal vessels of the vascular zone during the critical period of initial placenta development. The predominant cell population within these vessels is of the monocyte/macrophage lineage and expresses the mucosal integrin a4b7, which represents the ligand for MAdCAM-1; neutrophils and lymphocytes are rare. To directly assess the importance of identified adhesion receptors, we undertook longterm in vivo inhibition studies using monoclonal antibodies to inhibit the contribution of MAdCAM-1 in leukocyte trafficking to the decidua or to deplete a4b7 + leukocytes. In addition, implantation sites of mouse strains genetically deficient in specific adhesion receptors were investigated. Our results underline the importance of predicted adhesion pathways in the recruitment of monocyte-like cells, especially those expressing a4b7. Interestingly, maternal/ fetal units with inhibited recruitment of a4b7 + leukocytes or the absence of these cells are characterized by reduced size and frequency of uterine NK cells.

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Section: Discussionmentioning

confidence: 99%

“…Female and male b7-integrin -/-(C57BL/6-Itgb7 tm1Cgn ) [16] and P-selectin -/-(C57BL/6; 129S-Selp tm1Hyn ) [17] mice were obtained from the Jackson Laboratory. Females were mated by overnight cohabitation with males (BALB/c females with C57BL/6J males and P-selectin -/-, b7 -/-and C57BL/6J females with syngeneic males).…”

Section: Micementioning

confidence: 99%

Functional involvement of P‐selectin and MAdCAM‐1 in the recruitment of α4β7‐integrin‐expressing monocyte‐like cells to the pregnant mouse uterus

et al. 2004

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“…Indeed, administration of mAbs specific for MAdCAM-1 or the additional MAdCAM-1 receptors, ␣ 4 ␤ 1 integrin, and ␣ 4 ␤ 7 integrin effectively inhibits the progression of insulitis and the development of overt diabetes in NOD mice (19,36,41). A comparison of NOD mice lacking ␤ 7 integrins, CD62L, or both could be used to further dissect the relative contribution of these adhesion molecules in T1D (42,43).…”

Section: Discussionmentioning

confidence: 99%

L-Selectin Is Not Required for T Cell-Mediated Autoimmune Diabetes

Friedline

Wong

Steeber

et al. 2002

The Journal of Immunology

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Administration of anti-L-selectin (CD62L) mAb to neonatal nonobese diabetic (NOD) mice mediates long term protection against the development of insulitis and overt diabetes. These results suggested that CD62L has a key role in the general function of β cell-specific T cells. To further examine the role of CD62L in the development of type 1 diabetes, NOD mice lacking CD62L were established. The onset and frequency of overt diabetes were equivalent among CD62L+/+, CD62L+/−, and CD62L−/− NOD littermates. Furthermore, patterns of T cell activation, migration, and β cell-specific reactivity were similar in NOD mice of all three genotypes. Adoptive transfer experiments with CD62L−/− CD4+ T cells prepared from BDC2.5 TCR transgenic mice revealed no apparent defects in migration to pancreatic lymph nodes, proliferation in response to β cell Ag, or induction of diabetes in NOD.scid recipients. In conclusion, CD62L expression is not essential for the development of type 1 diabetes in NOD mice.

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“…In pLNs L-selectin/CD62L on lymphoid cells recognizes the carbohydrate ligand peripheral node addressin (PNAd) (1,2), whereas homing to Peyer's patches (PPs) is initiated by the binding of a 4 b 7 integrin on leukocytes to mucosal addressin cell adhesion molecule 1 (MAdCAM-1) on endothelial cells (3)(4)(5)(6)(7)(8). In mesenteric LNs (mLNs) a combined mechanism operates by which MAdCAM-1 and PNAd, both expressed on HEVs, serve as endothelial receptors for extravasation (9).…”

Section: Ymphocyte Homing To Peripheral Lymph Nodes (Plns) Andmentioning

confidence: 99%

Absence of Nkx2-3 Homeodomain Transcription Factor Reprograms the Endothelial Addressin Preference for Lymphocyte Homing in Peyer’s Patches

Kellermayer

Mihalj

Lábadi

et al. 2014

The Journal of Immunology

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Although the homing of lymphocytes to GALT has been extensively studied, little is known about how high endothelial venules (HEVs) within Peyer’s patches (PPs) are patterned to display dominantly mucosal addressin cell adhesion molecule 1 (MAdCAM-1). In this study, we report that Nkx2-3–deficient mice show gradual loss of MAdCAM-1 in PPs postnatally and increased levels of mRNA for peripheral lymph node addressin (PNAd) backbone proteins as well as enhanced expression of MECA79 sulfated glycoepitope at the luminal aspect of HEVs, thus replacing MAdCAM-1 with PNAd. Induction of PNAd in mutant PPs requires lymphotoxin β receptor activity, and its upregulation needs the presence of mature T and B cells. Furthermore, treatment with MECA-79 anti-PNAd mAb in vivo effectively blocks lymphocyte homing to mutant PPs. Despite the replacement of MAdCAM-1 by PNAd in HEV endothelia, lymphocytes could efficiently home to PPs in mutant mice. We conclude that although Nkx2-3 activity controls the addressin balance of HEVs in GALT, the general HEV functionality is preserved independently from Nkx2-3, indicating a substantial plasticity in the specification of GALT HEV endothelium.

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Critical role for β7 integrins in formation of the gut-associated lymphoid tissue

Cited by 532 publications

References 28 publications

Functional involvement of P‐selectin and MAdCAM‐1 in the recruitment of α4β7‐integrin‐expressing monocyte‐like cells to the pregnant mouse uterus

Functional involvement of P‐selectin and MAdCAM‐1 in the recruitment of α4β7‐integrin‐expressing monocyte‐like cells to the pregnant mouse uterus

L-Selectin Is Not Required for T Cell-Mediated Autoimmune Diabetes

Absence of Nkx2-3 Homeodomain Transcription Factor Reprograms the Endothelial Addressin Preference for Lymphocyte Homing in Peyer’s Patches

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