Molecular Evidence for a Thymus-Independent Partial T Cell Development in a FOXN1−/− Athymic Human Fetus

Fusco, Anna; Panico, Luigi; Gorrese, Marisa; Bianchino, Gabriella; Barone, Maria Vittoria; Grieco, Vitina; Vitiello, Laura; D’Assante, Roberta; Romano, Rosa; Palamaro, Loredana; Scalia, Giulia; Vecchio, Luigi Del; Pignata, Claudio

doi:10.1371/journal.pone.0081786

Cited by 6 publications

(7 citation statements)

References 38 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…69,70 The appearance of human gut Vγ4 cells may also occur independently of the thymus, but the ontogeny of these human cells is still not well addressed. 71 Thus, the contribution of gut-resident γδ T cell development from the thymus seems minimal.…”

Section: De Velopment Of Circul Ating and G Ut-re S Ident γδ T Cell Smentioning

confidence: 99%

“…However, nude mice, which lack a thymus, still contain Vγ7 cells, 1,66‐68 and parabiosis experiments using adult mice have demonstrated that Vγ7 cells are rarely replaced by circulating cells 69,70 . The appearance of human gut Vγ4 cells may also occur independently of the thymus, but the ontogeny of these human cells is still not well addressed 71 . Thus, the contribution of gut‐resident γδ T cell development from the thymus seems minimal.…”

Section: Development Of Circulating and Gut‐resident γδ T Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Gut γδ T cells as guardians, disruptors, and instigators of cancer

Suzuki

Hayman

Kilbey

et al. 2020

Immunological Reviews

View full text Add to dashboard Cite

One of the most prevalent immune cell populations in gut tissue are γδ T cells. γδ T cells represent a collection of diverse subsets with independent phenotypes and functions-some subsets reside in tissue-resident and other subsets circulate in blood. In humans, these subsets are defined by their expression of the δ chain (Vδ1, Vδ2, and Vδ3), whereas γδ T cell subsets in mice are characterized by the expression of the γ chain (Vγ1, Vγ4, Vγ5, Vγ6, and Vγ7). One interesting aspect of γδ T cells is that the γδTCR often dictates where the cells localize anatomically. Human Vδ1 and Vδ3 cells are frequently found in organs, including the gut, skin, and liver, 1-3 while Vδ2 cells circulate in the peripheral blood. Similarly, mouse Vγ5, Vγ6, and Vγ7 cells are tissue-resident, whereas Vγ1 and Vγ4 cells traffic from tissue to lymph nodes. Human Vγ4Vδ1 cells and mouse Vγ7 cells account for the majority of gut-resident γδ T cells, 1,4 but other subsets can infiltrate diseased, damaged, and dysplastic gut

show abstract

Section: De Velopment Of Circul Ating and G Ut-re S Ident γδ T Cell Smentioning

confidence: 99%

Section: Development Of Circulating and Gut‐resident γδ T Cellsmentioning

confidence: 99%

Gut γδ T cells as guardians, disruptors, and instigators of cancer

Suzuki

Hayman

Kilbey

et al. 2020

Immunological Reviews

View full text Add to dashboard Cite

show abstract

“…Conversely, the production of CD8 + naive lymphocytes after BMT is less thymus dependent and even occurs in nude/SCID patients. In addition, a recent study showed the presence of T lymphocytes in a FOXN1 –/– human fetus, suggesting partial T cell ontogeny in a thymus‐ and FOXN1‐independent process . Thymus transplantation has been shown to lead to immune reconstitution in two nude/SCID patients affected with disseminated Bacillus Calmette‐Guérin infection and cytopenia …”

Section: Scid Due To Thymic Abnormalities: From Digeorge Syndrome To mentioning

confidence: 99%

“…In addition, a recent study showed the presence of T lymphocytes in a FOXN1 -/human fetus, suggesting partial T cell ontogeny in a thymus-and FOXN1independent process. 90 Thymus transplantation has been shown to lead to immune reconstitution in two nude/SCID patients affected with disseminated Bacillus Calmette-Guérin infection and cytopenia. 91 Before the identification of human nude/SCID, the DiGeorge syndrome (DGS) was long considered the model of a severe T cell differentiation defect.…”

Section: Scid Due To Thymic Abnormalities: From Digeorge Syndrome To mentioning

confidence: 99%

Severe combined immunodeficiency—an update

Cirillo

Giardino

Gallo

et al. 2015

Annals of the New York Academy of Sciences

Self Cite

View full text Add to dashboard Cite

Severe combined immunodeficiencies (SCIDs) are a group of inherited disorders responsible for severe dysfunctions of the immune system. These diseases are life-threatening when the diagnosis is made too late; they are the most severe forms of primary immunodeficiency. SCID patients often die during the first two years of life if appropriate treatments to reconstitute their immune system are not undertaken. Conventionally, SCIDs are classified according either to the main pathway affected by the molecular defect or on the basis of the specific immunologic phenotype that reflects the stage where the blockage occurs during the differentiation process. However, during the last few years many new causative gene alterations have been associated with unusual clinical and immunological phenotypes. Many of these novel forms of SCID also show extra-hematopoietic alterations, leading to complex phenotypes characterized by a functional impairment of several organs, which may lead to a considerable delay in the diagnosis. Here we review the biological and clinical features of SCIDs paying particular attention to the most recently identified forms and to their unusual or extra-immunological clinical features.

show abstract

“…Most of the T-cells bear TCRγ δ instead of TCRαβ [45] and, although altered, the TCR gene rearrangement occurs in the absence of the thymus, suggesting an extrathymic site of differentiation for TCR chains, which is FOXN1-independent. Indeed, recent evidence suggests that, during embryogenesis, in the absence of FOXN1, a partial T-cell development can occur at extrathymic sites [46]. The Nude/SCID syndrome is more severe than the DiGeorge Syndrome, an immunodeficiency due to a complete or partial absence of the thymus, not associated with hairlessness or gross abnormalities in skin annexa.…”

Section: The Nude/scid Syndrome and Its Associated Skin Abnormalitiesmentioning

confidence: 99%

Unraveling the Link Between Ectodermal Disorders and Primary Immunodeficiencies

D’Assante

Fusco

Palamaro

et al. 2015

International Reviews of Immunology

Self Cite

View full text Add to dashboard Cite

Primary immunodeficiencies (PIDs) include a heterogeneous group of mostly monogenic diseases characterized by functional/developmental alterations of the immune system. Skin and skin annexa abnormalities may be a warning sign of immunodeficiency, since both epidermal and thymic epithelium have ectodermal origin. In this review, we will focus on the most common immune disorders associated with ectodermal alterations. Elevated IgE levels represent the immunological hallmark of hyper-IgE syndrome, characterized by severe eczema and susceptibility to infections. Ectodermal dysplasia (ED) is a group of rare disorders that affect tissues of ectodermal origin. Hypoidrotic ED (HED), the most common form, is inherited as autosomal dominant, autosomal recessive or X-linked trait (XLHED). HED and XLHED are caused by mutations in NEMO and EDA-1 genes, respectively, and show similarities in the cutaneous involvement but differences in the susceptibility to infections and immunological phenotype. Alterations in the transcription factor FOXN1 gene, expressed in the mature thymic and skin epithelia, are responsible for human and murine athymia and prevent the development of the T-cell compartment associated to ectodermal abnormalities such as alopecia and nail dystrophy. The association between developmental abnormalities of the skin and immunodeficiencies suggest a role of the skin as a primary lymphoid organ. Recently, it has been demonstrated that a co-culture of human skin-derived keratinocytes and fibroblasts, in the absence of thymic components, can support the survival of human haematopoietic stem cells and their differentiation into T-lineage committed cells.

show abstract

Molecular Evidence for a Thymus-Independent Partial T Cell Development in a FOXN1−/− Athymic Human Fetus

Cited by 6 publications

References 38 publications

Gut γδ T cells as guardians, disruptors, and instigators of cancer

Gut γδ T cells as guardians, disruptors, and instigators of cancer

Severe combined immunodeficiency—an update

Unraveling the Link Between Ectodermal Disorders and Primary Immunodeficiencies

Contact Info

Product

Resources

About