Regulating human Th17 cells via differential expression of IL-1 receptor.

In humans, interleukin-1beta (IL-1beta) has been suggested as an essential cytokine for developing IL-17- or IL-17A-producing CD4(+) T helper 17 (Th17) cells. However, little is known about the relationship of IL-1 receptor expression and Th17 cell differentiation. We report here the presence of 2 distinct CD4(+) T-cell populations with and without expression of IL-1RI that correlates with the capacity to produce IL-17 in naive and memory CD4(+) T cells of human peripheral blood. IL-1RI(+) memory CD4(+) T cells had increased gene expression of IL17, RORC, and IRF4 even before T-cell receptor triggering, indicating that the effect of IL-1beta is programmed in these cells via IL-1RI. Although CD4(+) T cells from umbilical cord blood did not express IL-1RI, the cytokines IL-7, IL-15, and transforming growth factor-beta (TGF-beta) up-regulated IL-1RI expression on naive CD4(+) T cells, suggesting that IL-1RI(+) naive CD4(+) T cells develop in periphery. Furthermore, IL-17 production from the cytokine-treated naive CD4(+) T cells was induced by IL-1beta and this induction was blocked by IL-1R antagonist. These results indicate that human Th17 cell differentiation is regulated via differential expression of IL-1RI, which is controlled by IL-7 and IL-15.

[1]  A. E. Sousa,et al.  IL-7 sustains CD31 expression in human naive CD4+ T cells and preferentially expands the CD31+ subset in a PI3K-dependent manner. , 2009, Blood.

[2]  S. Gaffen.  An overview of IL-17 function and signaling. , 2008, Cytokine.

[3]  L. Cosmi,et al.  Human interleukin 17–producing cells originate from a CD161+CD4+ T cell precursor , 2008, The Journal of experimental medicine.

[4]  J. Dayer,et al.  IL-21 promotes survival and maintains a naive phenotype in human CD4+ T lymphocytes. , 2008, International immunology.

[5]  Lars Rogge,et al.  Faculty Opinions recommendation of IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. , 2008 .

[6]  V. Kuchroo,et al.  Induction and effector functions of TH17 cells , 2008, Nature.

[7]  S. Chevalier,et al.  Chronically Inflamed Human Tissues Are Infiltrated by Highly Differentiated Th17 Lymphocytes , 2008, The Journal of Immunology.

[8]  E. Barillot,et al.  A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses , 2008, Nature Immunology.

[9]  Chen Dong,et al.  TH17 cells in development: an updated view of their molecular identity and genetic programming , 2008, Nature Reviews Immunology.

[10]  M. McGeachy,et al.  Review Th17 Cell Differentiation: the Long and Winding Road , 2022 .

[11]  J. O’Shea,et al.  Regulation of IL-17 production in human lymphocytes. , 2008, Cytokine.

[12]  Chen Dong,et al.  T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. , 2008, Immunity.

[13]  K. Tracey,et al.  IL-1α and IL-1β Are Endogenous Mediators Linking Cell Injury to the Adaptive Alloimmune Response1 , 2007, The Journal of Immunology.

[14]  D. Hommes,et al.  Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. , 2007, Immunity.

[15]  C. Tato,et al.  Distinct regulation of interleukin-17 in human T helper lymphocytes. , 2007, Arthritis and rheumatism.

[16]  T. Mak,et al.  The development of inflammatory TH-17 cells requires interferon-regulatory factor 4 , 2007, Nature Immunology.

[17]  D. Levy,et al.  IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways , 2007, Nature Immunology.

[18]  Kathleen M. Smith,et al.  Development, cytokine profile and function of human interleukin 17–producing helper T cells , 2007, Nature Immunology.

[19]  D. Jarrossay,et al.  Surface phenotype and antigenic specificity of human interleukin 17–producing T helper memory cells , 2007, Nature Immunology.

[20]  I. Kang,et al.  Down-Regulation of IL-7Rα Expression in Human T Cells via DNA Methylation1 , 2007, The Journal of Immunology.

[21]  I. Kang,et al.  Down-regulation of IL-7Ralpha expression in human T cells via DNA methylation. , 2007, Journal of immunology.

[22]  F. Sallusto,et al.  Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. , 2007, Nature immunology.

[23]  K. Tracey,et al.  IL-1alpha and IL-1beta are endogenous mediators linking cell injury to the adaptive alloimmune response. , 2007, Journal of immunology.

[24]  D. Littman,et al.  The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells , 2006, Cell.

[25]  P. Burkett,et al.  Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. , 2006, Annual review of immunology.

[26]  D. Littman,et al.  The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. , 2006, Cell.

[27]  R. D. Hatton,et al.  Transforming growth factor-beta induces development of the T(H)17 lineage. , 2006, Nature.

[28]  A. Lindén,et al.  Interleukin-17 family members and inflammation. , 2004, Immunity.

[29]  C. Stansberg,et al.  The interleukin 1 receptor family. , 2004, Developmental and comparative immunology.

[30]  C. Dinarello,et al.  The IL-1 family and inflammatory diseases. , 2002, Clinical and experimental rheumatology.

[31]  J. Lowenthal,et al.  Measurement of lymphokine receptors. , 2001, Current protocols in immunology.

[32]  D. Boraschi,et al.  The type II IL-1 receptor interacts with the IL-1 receptor accessory protein: a novel mechanism of regulation of IL-1 responsiveness. , 1998, Journal of immunology.

[33]  W. Falk,et al.  A critical role for interleukin‐1 receptor accessory protein in interleukin‐1 signaling , 1997, European journal of immunology.

[34]  A. Mantovani,et al.  The type II 'decoy' receptor: a novel regulatory pathway for interleukin 1. , 1994, Immunology today.

[35]  A. Taylor-Robinson,et al.  Expression of the IL-1 receptor discriminates Th2 from Th1 cloned CD4+ T cells specific for Plasmodium chabaudi. , 1994, Immunology.

[36]  M. Luqman,et al.  Differential effect of interleukin 1 on naive and memory CD4+ T cells , 1992, European journal of immunology.

[37]  S. Eto,et al.  Expression of interleukin 1 receptors on human peripheral T cells. , 1987, Journal of immunology.

[38]  S. Dower,et al.  Similarity between the interleukin 1 receptors on a murine T-lymphoma cell line and on a murine fibroblast cell line. , 1986, Proceedings of the National Academy of Sciences of the United States of America.