Functional Assessment of  α<sub>E</sub>β<sub>7</sub>/E‐cadherin Interactions in the Steady State Postnatal Thymus

Prockop, Susan E.; Petrie, Howard T.

doi:10.1080/10446670410001722212

Cited by 5 publications

(5 citation statements)

References 34 publications

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“…5). This finding demonstrates the relevance of the thymic microenvironment in governing precursor cell recruitment, supporting other previous results [6,35]. In these assays, the expression of EphB2LacZ in the thymic cells also provides important improvement in WT progenitor cell recruitment, although the differences remain statistically significant compared with the WT thymuses.…”

Section: Discussionsupporting

confidence: 89%

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EphB2 and EphB3 play an important role in the lymphoid seeding of murine adult thymus

Alfaro

García‐Ceca

Farias-de-Oliveira

et al. 2015

Journal of Leukocyte Biology

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Adult thymuses lacking either ephrin type B receptor 2 (EphB2) or EphB3, or expressing a truncated form of EphB2, the forward signal-deficient EphB2LacZ, have low numbers of early thymic progenitors (ETPs) and are colonized in vivo by reduced numbers of injected bone marrow (BM) lineage-negative (Lin(-)) cells. Hematopoietic progenitors from these EphB mutants showed decreased capacities to colonize wild type (WT) thymuses compared with WT precursors, with EphB2(-/-) cells exhibiting the greatest reduction. WT BM Lin(-) cells also showed decreased colonizing capacity into mutant thymuses. The reduction was also more severe in EphB2(-/-) host thymuses, with a less severe phenotype in the EphB2LacZ thymus. These results suggest a major function for forward signaling through EphB2 and, to a lesser extent, EphB3, in either colonizing progenitor cells or thymic stromal cells, for in vivo adult thymus recruitment. Furthermore, the altered expression of the molecules involved in thymic colonization that occurs in the mutant thymus correlates with the observed colonizing capacities of different mutant mice. Reduced production of CCL21 and CCL25 occurred in the thymus of the 3 EphB-deficient mice, but their expression, similar to that of P-selectin, on blood vessels, the method of entry of progenitor cells into the vascular thymus, only showed a significant reduction in EphB2(-/-) and EphB3(-/-) thymuses. Decreased migration into the EphB2(-/-) thymuses correlated also with reduced expression of both ephrinB1 and ephrinB2, without changes in the EphB2LacZ thymuses. In the EphB3(-/-) thymuses, only ephrinB1 expression appeared significantly diminished, confirming the relevance of forward signals mediated by the EphB2-ephrinB1 pair in cell recruitment into the adult thymus.

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Section: Discussionsupporting

confidence: 89%

“…The relevance of a thymic microenvironment for BM progenitor cell colonization previously claimed [6,13,35] was evidenced after i.v. injection of 10 6 WT cell progenitors in EphB-deficient mice.…”

Section: Migration Of Wt Bm Progenitor Cells Into Ephb-deficient Thymuses Is Profoundly Reducedmentioning

confidence: 91%

EphB2 and EphB3 play an important role in the lymphoid seeding of murine adult thymus

Alfaro

García‐Ceca

Farias-de-Oliveira

et al. 2015

Journal of Leukocyte Biology

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“…It is possible that, in patients with specific genetic variants of SCID, there is a competitive inhibition of engraftment of normal donor-derived hematopoietic progenitors by defective host progenitors for occupancy of one or more of the specialized niches in the thymus or bone marrow [50,51]. In murine models, such resistance to the development of normal precursors within the thymus has been demonstrated in RAG-2 −/− and TCR B −/− but not γc −/− or IL7Rα −/− forms of SCID [52]. Age at transplant is not a factor in B cell chimerism or B cell function and neither is race or sex [3].…”

Section: Discussionmentioning

confidence: 99%

Post-Transplantation B Cell Function in Different Molecular Types of SCID

et al. 2012

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Purpose Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic cause characterized by profound deficiencies of T, B and sometimes NK cell function. Non-ablative HLA-identical or rigorously T cell-depleted haploidentical parental bone marrow transplantation (BMT) results in thymus-dependent genetically donor T cell development in the recipients, leading to a high rate of long-term survival. However, the development of B cell function has been more problematic. We report here results of analyses of B cell function in 125 SCID recipients prior to and long-term after non-ablative BMT, according to their molecular type. Methods Studies included blood immunoglobulin measurements; antibody titers to standard vaccines, blood group antigens and bacteriophage Φ × 174; flow cytometry to examine for markers of immaturity, memory, switched memory B cells and BAFF receptor expression; B cell chimerism; B cell spectratyping; and B cell proliferation. Results The results showed that B cell chimerism was not required for normal B cell function in IL7Rα-Def, ADA-Def and CD3-Def SCIDs. In X-linked-SCID, Jak3-Def SCID and those with V-D-J recombination defects, donor B cell chimerism was necessary for B cell function to develop. Conclusion The most important factor determining whether B cell function develops in SCID T cell chimeras is the underlying molecular defect. In some types, host B cells function normally. In those molecular types where host B cell function did not develop, donor B cell chimerism was necessary to achieve B cell function. 236 words

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“…Though E-cadherin was originally defi ned by its homophilic binding, the ability to partner with other proteins expands its functional repertoire. These interactions can be between other adhesion proteins such as N-cadherin (Ounkomol et al, 2010) and integrins (Prockop & Petrie, 2004), which are mediators of cell -substratum adhesion. The latter interaction may provide the basis by which E-cadherin levels can mediate tissue infl ammation.…”

Section: E-cadherin Signaling and Mechanotransductionmentioning

confidence: 99%

Signaling and Mechanical Roles of E-cadherin

Bhatt

Rizvi

Batta

et al. 2013

Cell Communication & Adhesion

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The epithelium comprises an important tissue that lines the internal and external surfaces of metazoan organs. In order to organize sheets of epithelial cells into three-dimensional tissues, it requires the coordination of basic cellular processes such as polarity, adhesion, growth, and differentiation. Moreover, as a primary barrier to the external environment, epithelial tissues are often subjected to physical forces and damage. This critical barrier function dictates that these fundamental cellular processes are continually operational in order to maintain tissue homeostasis in the face of almost constant trauma and stress. A protein that is largely responsible for the organization and maintenance of epithelial tissues is the transmembrane protein, E-cadherin, found at the surface of epithelial cells. Though originally investigated for its essential role in mediating intercellular cohesion, its impact on a wide array of physiological processes underscores its fundamental contributions to tissue development and its perturbation in a variety of common diseases.

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Functional Assessment of α_Eβ₇/E‐cadherin Interactions in the Steady State Postnatal Thymus

Cited by 5 publications

References 34 publications

EphB2 and EphB3 play an important role in the lymphoid seeding of murine adult thymus

EphB2 and EphB3 play an important role in the lymphoid seeding of murine adult thymus

Post-Transplantation B Cell Function in Different Molecular Types of SCID

Signaling and Mechanical Roles of E-cadherin

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Functional Assessment of αEβ7/E‐cadherin Interactions in the Steady State Postnatal Thymus

Cited by 5 publications

References 34 publications

EphB2 and EphB3 play an important role in the lymphoid seeding of murine adult thymus

EphB2 and EphB3 play an important role in the lymphoid seeding of murine adult thymus

Post-Transplantation B Cell Function in Different Molecular Types of SCID

Signaling and Mechanical Roles of E-cadherin

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Functional Assessment of α_Eβ₇/E‐cadherin Interactions in the Steady State Postnatal Thymus