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Polysialic Acid Governs T-Cell Development by Regulating Progenitor Access to the Thymus

Drake, Penelope M. ; Stock, Christina M. ; Nathan, Jay K. ; Gip, Phung ; Golden, Kevin P. K. ; Weinhold, Birgit ; Gerardy-Schahn, Rita ; Bertozzi, Carolyn R.

Proceedings of the National Academy of Sciences - PNAS, 2009-07, Vol.106 (29), p.11995-12000 [Periódico revisado por pares]

United States: National Academy of Sciences

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Título:
Polysialic Acid Governs T-Cell Development by Regulating Progenitor Access to the Thymus
Autor: Drake, Penelope M. ; Stock, Christina M. ; Nathan, Jay K. ; Gip, Phung ; Golden, Kevin P. K. ; Weinhold, Birgit ; Gerardy-Schahn, Rita ; Bertozzi, Carolyn R.
Assuntos: Animals ; Biochemistry ; Biological Assay ; Biological Sciences ; Blood ; Bone marrow ; Cell adhesion & migration ; Cell Lineage ; Cell Movement ; Cell Size ; Cytokines ; Cytometry ; Endocrine system ; Hematopoietic stem cells ; Immune system ; Immunology ; Lymphocyte Subsets - cytology ; Mice ; Neural cell adhesion molecules ; Physiological regulation ; Progenitor cells ; Sialic Acids - metabolism ; Sialyltransferases - deficiency ; Sialyltransferases - metabolism ; Stem Cell Niche - cytology ; Stem Cell Niche - enzymology ; Stem Cells - cytology ; Stem Cells - enzymology ; T cell receptors ; T lymphocytes ; T-Lymphocytes - cytology ; T-Lymphocytes - enzymology ; Thymocytes ; Thymus Gland - cytology ; Thymus Gland - enzymology ; Thymus Gland - growth & development ; Time Factors
É parte de: Proceedings of the National Academy of Sciences - PNAS, 2009-07, Vol.106 (29), p.11995-12000
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Author contributions: P.M.D. designed research; P.M.D., C.M.S., J.K.N., P.G., and K.P.K.G. performed research; B.W. and R.G.-S. contributed new reagents/analytic tools; P.M.D. analyzed data; and P.M.D. and C.R.B. wrote the paper.
Contributed by Carolyn R. Bertozzi, May 12, 2009
Descrição: Although the polysialyltransferase ST8Sia IV is expressed in both primary and secondary human lymphoid organs, its product, polysialic acid (polySia), has been largely overlooked by immunologists. In contrast, polySia expression and function in the nervous system has been well characterized. In this context, polySia modulates cellular adhesion, migration, cytokine response, and contactdependent differentiation. Provocatively, these same processes are vital components of immune development and function. We previously established that mouse multipotent hematopoietic progenitors use ST8Sia IV to express polySia on their cell surfaces. Here, we demonstrate that, relative to wild-type controls, $st8SiaIV^{ - / - } $ mice have a 30% reduction in total thymocytes and a concomitant deficiency in the earliest thymocyte precursors. T-cell progenitors originate in the bone marrow and are mobilized to the blood at regular intervals by unknown signals. We performed in vivo reconstitution experiments in which $st8SiaIV^{ - / - } $ progenitors competed with wild-type cells to repopulate depleted or deficient immune subsets. Progenitors lacking polySi exhibited a specific defect in T-cell development because of an inability to access the thymus. This phenotype probably reflects a decreased capacity of the $st8SiaIV^{ - / - } $ progenitors to escape from the bone marrow niche. Collectively, these results provide evidence that polySia is involved in hematopoietic development.
Editor: United States: National Academy of Sciences
Idioma: Inglês

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Polysialic Acid Governs T-Cell Development by Regulating Progenitor Access to the Thymus

Drake, Penelope M. ; Stock, Christina M. ; Nathan, Jay K. ; Gip, Phung ; Golden, Kevin P. K. ; Weinhold, Birgit ; Gerardy-Schahn, Rita ; Bertozzi, Carolyn R.

United States: National Academy of Sciences

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