Mucosal Addressin Cell-Adhesion Molecule-1 Controls Plasma-Cell Migration and Function in the Small Intestine of Mice

Schippers, Angela; Leuker, Christoph E.; Pabst, Oliver; Kochut, Annika; Prochnow, Blair; Gruber, Achim D.; Leung, Euphemia; Krissansen, Geoffrey W.; Wagner, Norbert; Müller, Werner

doi:10.1053/j.gastro.2009.05.039

Cited by 37 publications

(35 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3 2/2 mutant spleen during the first two postnatal weeks when the white pulp and marginal zone architecture is established (25,44,45,50), it is reasonable to assume that loss of additional, yet unidentified, proteins contributes to the adult spleen phenotype in this mutation. This view is in line with the observation that MAdCAM-1-deficient mice exhibit apparently no major alterations of the splenic architecture (51). Importantly, the regulation of MAdCAM-1 expression by Nkx2-3 appears to be different for endothelial cells and other cells, such as FDCs, because FDC-associated MAdCAM-1 expression is preserved in mutant Peyer's patches (20), whereas the HEV-associated MAdCAM-1 production is abolished, similarly to HEVs in mLNs.…”

Section: Discussionsupporting

confidence: 75%

Transcription Factor Nkx2-3 Controls the Vascular Identity and Lymphocyte Homing in the Spleen

Czömpöly

Lábadi

Kellermayer

et al. 2011

The Journal of Immunology

View full text Add to dashboard Cite

The vasculature in the spleen and peripheral lymph nodes (pLNs) is considerably different, which affects both homing of lymphocytes and antigenic access to these peripheral lymphoid organs. In this paper, we demonstrate that in mice lacking the homeodomain transcription factor Nkx2-3, the spleen develops a pLN-like mRNA expression signature, coupled with the appearance of high endothelial venules (HEVs) that mediate L-selectin–dependent homing of lymphocytes into the mutant spleen. These ectopic HEV-like vessels undergo postnatal maturation and progressively replace MAdCAM-1 by pLN addressin together with the display of CCL21 arrest chemokine in a process that is reminiscent of HEV formation in pLNs. Similarly to pLNs, development of HEV-like vessels in the Nkx2-3–deficient spleen depends on lymphotoxin-β receptor-mediated signaling. The replacement of splenic vessels with a pLN-patterned vasculature impairs the recirculation of adoptively transferred lymphocytes and reduces the uptake of blood-borne pathogens. The Nkx2-3 mutation in BALB/c background causes a particularly disturbed splenic architecture, characterized by the near complete lack of the red pulp, without affecting lymph nodes. Thus, our observations reveal that the organ-specific patterning of splenic vasculature is critically regulated by Nkx2-3, thereby profoundly affecting the lymphocyte homing mechanism and blood filtering capacity of the spleen in a tissue-specific manner.

show abstract

Section: Discussionsupporting

confidence: 75%

Transcription Factor Nkx2-3 Controls the Vascular Identity and Lymphocyte Homing in the Spleen

Czömpöly

Lábadi

Kellermayer

et al. 2011

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Adhesion molecules are important for the proper localization of PC. For example, α4β7 integrin is critical for IgA-secreting cells to home to the gut5051. Spleen-derived IgG ASC are known to highly express α4β1 and αLβ2 integrins, both of which are important for bone marrow homing2122.…”

Section: Discussionmentioning

confidence: 99%

Shp1 signalling is required to establish the long-lived bone marrow plasma cell pool

et al. 2014

Nat Commun

View full text Add to dashboard Cite

Germline or B-cell-specific loss of Ptpn6 gene encoding the Shp1 protein tyrosine phosphatase leads to skewed B lymphopoiesis and systemic autoimmunity. Here, to study its role in B-cell terminal differentiation, we generated Ptpn6f/fAicdaCre/+ mice with Shp1 ablated only in activated B cells. We show that Ptpn6f/fAicdaCre/+ mice have normal B-cell development but exhibit defective class-switched primary and recalled antibody response to a T-cell-dependent antigen. Germinal centres are present but do not persist and memory B cells are not formed. Interestingly, Shp1-deficient plasma cells are generated in the spleen but do not contribute to the bone marrow long-lived pool. Plasma cells lacking Shp1 exhibit aberrant α4β1 integrin activation due to dysregulated Src- and PI3-kinase signalling and manifest attenuated migration in vitro and defective bone marrow homing when reconstituted in vivo. Interrupting α4β1–VCAM-1 interaction rectifies this defect. These data suggest that Shp1 signalling is required for the establishment of a life-long protective humoral immunity.

show abstract

“…Mice OT-II Ly5.1 mice, C57BL/6-Itgb7 tm1Cgn /J (ITGB7-deficient mice), MADCAM1-deficient mice (Schippers et al, 2009), B6.129P-Cx3cr1 tm1Litt /J and BALB/ c.129P-Cx3cr1 tm1Litt /J (CX3CR1-deficient mice on C57BL/6 and BALB/c backgrounds, respectively), and DEREG mice expressing DTR receptor and GFP under control of the FoxP3 promotor (Lahl et al, 2007) were bred at the central animal facility of Hannover Medical School under specific-pathogenfree conditions. C57BL/6 and BALB/c mice were additionally purchased from Charles River Laboratory.…”

Section: Methodsmentioning

confidence: 99%

Intestinal Tolerance Requires Gut Homing and Expansion of FoxP3+ Regulatory T Cells in the Lamina Propria

et al. 2011

Self Cite

View full text Add to dashboard Cite

Tolerance to food antigen manifests in the absence and/or suppression of antigen-specific immune responses locally in the gut but also systemically, a phenomenon known as oral tolerance. Oral tolerance is thought to originate in the gut-draining lymph nodes, which support the generation of FoxP3(+) regulatory T (Treg) cells. Here we use several mouse models to show that Treg cells, after their generation in lymph nodes, need to home to the gut to undergo local expansion to install oral tolerance. Proliferation of Treg cells in the intestine and production of interleukin-10 by gut-resident macrophages was blunted in mice deficient in the chemokine (C-X3-C motif) receptor 1 (CX3CR1). We propose a model of stepwise oral tolerance induction comprising the generation of Treg cells in the gut-draining lymph nodes, followed by migration into the gut and subsequent expansion of Treg cells driven by intestinal macrophages.

show abstract

Mucosal Addressin Cell-Adhesion Molecule-1 Controls Plasma-Cell Migration and Function in the Small Intestine of Mice

Cited by 37 publications

References 35 publications

Transcription Factor Nkx2-3 Controls the Vascular Identity and Lymphocyte Homing in the Spleen

Transcription Factor Nkx2-3 Controls the Vascular Identity and Lymphocyte Homing in the Spleen

Shp1 signalling is required to establish the long-lived bone marrow plasma cell pool

Intestinal Tolerance Requires Gut Homing and Expansion of FoxP3+ Regulatory T Cells in the Lamina Propria

Contact Info

Product

Resources

About