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The interleukin-7 receptor α chain contributes to altered homeostasis of regulatory T cells in multiple sclerosis.
Eur J Immunol. 2011 Mar; 41(3):845-53.EJ

Abstract

Treg homeostasis is disturbed in multiple sclerosis (MS). Frequencies of recent thymic emigrant (RTE)-Treg are reduced and the disparity between RTE-Treg and long-lived memory Treg coincides with the MS-associated Treg defect, as shown previously. Recent studies demonstrate that IL-7 and thymic stromal lymphopoietin (TSLP) are critical for Treg maturation. Therefore, altered signaling through their receptors (IL-7R, TSLP receptor (TSLPR)), sharing the IL-7Rα-chain (IL-7Rα), might contribute to impaired Treg development. Using blood samples from 56 patients with MS and 33 healthy controls, we assessed IL-7Rα-expression on conventional T cells; frequencies, phenotypes and suppressive activities of Treg, plasma levels of IL-7 and soluble IL-7Rα; and screened for MS-associated IL-7RA gene polymorphism rs6897932. Moreover, we determined Treg expressing two different TCR Vα-chains designating thymus-originated cells. As TSLP/TSLPR signaling in thymic myeloid dendritic cells (MDCs) promotes Treg differentiation, we measured TSLPR expression on peripheral MDCs to indirectly test whether altered TSLPR expression might add to compromised Treg neogenesis. We found reduced IL-7Rα expression on conventional T cells and upregulated IL-7 plasma levels together with reduction of RTE-Treg frequencies and Treg function in MS, without clear genetic influence. Decreased IL-7Rα expression in MS correlated with declined dual-receptor-Treg and reduced MDC TSLPR expression, indicating contracted thymic Treg output. We suggest that altered IL-7R/TSLPR signaling contributes to impaired Treg neogenesis in MS, which is compensated by expanded memory-Treg and finally results in dysfunctional Treg.

Authors+Show Affiliations

Division of Molecular Neuroimmunology, Department of Neurology, University Hospital of Heidelberg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21287555

Citation

Haas, Jürgen, et al. "The Interleukin-7 Receptor Α Chain Contributes to Altered Homeostasis of Regulatory T Cells in Multiple Sclerosis." European Journal of Immunology, vol. 41, no. 3, 2011, pp. 845-53.
Haas J, Korporal M, Schwarz A, et al. The interleukin-7 receptor α chain contributes to altered homeostasis of regulatory T cells in multiple sclerosis. Eur J Immunol. 2011;41(3):845-53.
Haas, J., Korporal, M., Schwarz, A., Balint, B., & Wildemann, B. (2011). The interleukin-7 receptor α chain contributes to altered homeostasis of regulatory T cells in multiple sclerosis. European Journal of Immunology, 41(3), 845-53. https://doi.org/10.1002/eji.201041139
Haas J, et al. The Interleukin-7 Receptor Α Chain Contributes to Altered Homeostasis of Regulatory T Cells in Multiple Sclerosis. Eur J Immunol. 2011;41(3):845-53. PubMed PMID: 21287555.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The interleukin-7 receptor α chain contributes to altered homeostasis of regulatory T cells in multiple sclerosis. AU - Haas,Jürgen, AU - Korporal,Mirjam, AU - Schwarz,Alexander, AU - Balint,Bettina, AU - Wildemann,Brigitte, Y1 - 2011/02/01/ PY - 2010/10/06/received PY - 2010/11/17/revised PY - 2010/11/30/accepted PY - 2011/2/3/entrez PY - 2011/2/3/pubmed PY - 2011/4/13/medline SP - 845 EP - 53 JF - European journal of immunology JO - Eur. J. Immunol. VL - 41 IS - 3 N2 - Treg homeostasis is disturbed in multiple sclerosis (MS). Frequencies of recent thymic emigrant (RTE)-Treg are reduced and the disparity between RTE-Treg and long-lived memory Treg coincides with the MS-associated Treg defect, as shown previously. Recent studies demonstrate that IL-7 and thymic stromal lymphopoietin (TSLP) are critical for Treg maturation. Therefore, altered signaling through their receptors (IL-7R, TSLP receptor (TSLPR)), sharing the IL-7Rα-chain (IL-7Rα), might contribute to impaired Treg development. Using blood samples from 56 patients with MS and 33 healthy controls, we assessed IL-7Rα-expression on conventional T cells; frequencies, phenotypes and suppressive activities of Treg, plasma levels of IL-7 and soluble IL-7Rα; and screened for MS-associated IL-7RA gene polymorphism rs6897932. Moreover, we determined Treg expressing two different TCR Vα-chains designating thymus-originated cells. As TSLP/TSLPR signaling in thymic myeloid dendritic cells (MDCs) promotes Treg differentiation, we measured TSLPR expression on peripheral MDCs to indirectly test whether altered TSLPR expression might add to compromised Treg neogenesis. We found reduced IL-7Rα expression on conventional T cells and upregulated IL-7 plasma levels together with reduction of RTE-Treg frequencies and Treg function in MS, without clear genetic influence. Decreased IL-7Rα expression in MS correlated with declined dual-receptor-Treg and reduced MDC TSLPR expression, indicating contracted thymic Treg output. We suggest that altered IL-7R/TSLPR signaling contributes to impaired Treg neogenesis in MS, which is compensated by expanded memory-Treg and finally results in dysfunctional Treg. SN - 1521-4141 UR - https://www.unboundmedicine.com/medline/citation/21287555/The_interleukin_7_receptor_α_chain_contributes_to_altered_homeostasis_of_regulatory_T_cells_in_multiple_sclerosis_ L2 - https://doi.org/10.1002/eji.201041139 DB - PRIME DP - Unbound Medicine ER -