TSLP-activated Dendritic Cells Induce Human T Follicular Helper Cell Differentiation Through OX40-ligand

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2017 Apr 22

PMID 28428203

Citations 75

Authors

Lucia Pattarini

Coline Trichot

Sofia Bogiatzi

Maximilien Grandclaudon

Stephan Meller

Zela Keuylian

Melanie Durand

Elisabetta Volpe

Stefania Madonna

Andrea Cavani

Andrea Chiricozzi

Marco Romanelli

Toshiyuki Hori

Alain Hovnanian

Bernhard Homey

Vassili Soumelis

Affiliations

Soon will be listed here.

Abstract

T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells. TSLP-induced T cells expressed CXCR5, CXCL13, ICOS, PD1, BCL6, BTLA, and SAP, among other Tfh markers. Functionally, TSLP-DC-polarized T cells induced IgE secretion by memory B cells, and this depended on IL-4Rα. TSLP-activated DCs stimulated circulating memory Tfh cells to produce IL-21 and CXCL13. Mechanistically, TSLP-induced Tfh differentiation depended on OX40-ligand, but not on ICOS-ligand. Our results delineate a pathway of human Tfh differentiation in Th2 environments.

Citing Articles

HMOS 2'FL and 3FL prevent house dust mite induced proinflammatory cytokine release and decrease specific IgE production in a murine allergic asthma model.

Zuurveld M, de Kleer J, Berends A, Kooy M, Van Ark I, Leusink-Muis T Front Nutr. 2025; 12:1491430.

PMID: 40046758 PMC: 11879794. DOI: 10.3389/fnut.2025.1491430.

Tumor Microenvironment Drives the Cross-Talk Between Co-Stimulatory and Inhibitory Molecules in Tumor-Infiltrating Lymphocytes: Implications for Optimizing Immunotherapy Outcomes.

Franzese O Int J Mol Sci. 2024; 25(23).

PMID: 39684559 PMC: 11641238. DOI: 10.3390/ijms252312848.

Epithelial-immune interactions govern type 2 immunity at barrier surfaces.

Lopez Espinoza A, Christopher T, Tait Wojno E Curr Opin Immunol. 2024; 91():102501.

PMID: 39522453 PMC: 11734749. DOI: 10.1016/j.coi.2024.102501.

MERS-CoV Infection and Its Impact on the Expression of TSLP Cytokine and IgG Antibodies: An In Vivo and In Vitro Study.

Mubarak A, Alqoufail M, Almutairi S, Alrfaei B, Almotairi A, Aziz I Infect Drug Resist. 2024; 17:4589-4598.

PMID: 39469096 PMC: 11513571. DOI: 10.2147/IDR.S483133.

Thymic stromal lymphopoietin signaling in B cells from progenitors to plasma cells.

Domeier P, Ziegler S J Leukoc Biol. 2024; 117(2).

PMID: 39373526 PMC: 11878999. DOI: 10.1093/jleuko/qiae216.

References

Ma C, Avery D, Chan A, Batten M, Bustamante J, Boisson-Dupuis S . Functional STAT3 deficiency compromises the generation of human T follicular helper cells. Blood. 2012; 119(17):3997-4008. PMC: 3355712. DOI: 10.1182/blood-2011-11-392985. View

Jacquemin C, Schmitt N, Contin-Bordes C, Liu Y, Narayanan P, Seneschal J . OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response. Immunity. 2015; 42(6):1159-70. PMC: 4570857. DOI: 10.1016/j.immuni.2015.05.012. View

Liang H, Reinhardt R, Bando J, Sullivan B, Ho I, Locksley R . Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunity. Nat Immunol. 2011; 13(1):58-66. PMC: 3242938. DOI: 10.1038/ni.2182. View

Ito T, Wang Y, Duramad O, Hori T, Delespesse G, Watanabe N . TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J Exp Med. 2005; 202(9):1213-23. PMC: 2213234. DOI: 10.1084/jem.20051135. View

Nakazawa M, Sugi N, Kawaguchi H, Ishii N, Nakajima H, Minami M . Predominance of type 2 cytokine-producing CD4+ and CD8+ cells in patients with atopic dermatitis. J Allergy Clin Immunol. 1997; 99(5):673-82. DOI: 10.1016/s0091-6749(97)70030-7. View

Ramalingam T, Pesce J, Mentink-Kane M, Madala S, Cheever A, Comeau M . Regulation of helminth-induced Th2 responses by thymic stromal lymphopoietin. J Immunol. 2009; 182(10):6452-9. PMC: 2755487. DOI: 10.4049/jimmunol.0900181. View

Choi Y, Kageyama R, Eto D, Escobar T, Johnston R, Monticelli L . ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6. Immunity. 2011; 34(6):932-46. PMC: 3124577. DOI: 10.1016/j.immuni.2011.03.023. View

Furio L, Hovnanian A . Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy. Biol Chem. 2014; 395(9):945-58. DOI: 10.1515/hsz-2014-0137. View

Kusam S, Toney L, Sato H, Dent A . Inhibition of Th2 differentiation and GATA-3 expression by BCL-6. J Immunol. 2003; 170(5):2435-41. DOI: 10.4049/jimmunol.170.5.2435. View

10.

Wang Y, Ito T, Wang Y, Homey B, Watanabe N, Martin R . Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells. Immunity. 2006; 24(6):827-838. DOI: 10.1016/j.immuni.2006.03.019. View

11.

Tangye S, Ma C, Brink R, Deenick E . The good, the bad and the ugly - TFH cells in human health and disease. Nat Rev Immunol. 2013; 13(6):412-26. DOI: 10.1038/nri3447. View

12.

Locci M, Havenar-Daughton C, Landais E, Wu J, Kroenke M, Arlehamn C . Human circulating PD-1+CXCR3-CXCR5+ memory Tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses. Immunity. 2013; 39(4):758-69. PMC: 3996844. DOI: 10.1016/j.immuni.2013.08.031. View

13.

Trinchieri G . Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol. 2003; 3(2):133-46. DOI: 10.1038/nri1001. View

14.

Ying S, OConnor B, Ratoff J, Meng Q, Mallett K, Cousins D . Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J Immunol. 2005; 174(12):8183-90. DOI: 10.4049/jimmunol.174.12.8183. View

15.

Weinstein J, Lezon-Geyda K, Maksimova Y, Craft S, Zhang Y, Su M . Global transcriptome analysis and enhancer landscape of human primary T follicular helper and T effector lymphocytes. Blood. 2014; 124(25):3719-29. PMC: 4263981. DOI: 10.1182/blood-2014-06-582700. View

16.

Kim C, Lim H, Kim J, Rott L, Hillsamer P, Butcher E . Unique gene expression program of human germinal center T helper cells. Blood. 2004; 104(7):1952-60. DOI: 10.1182/blood-2004-03-1206. View

17.

Ueno H, Banchereau J, Vinuesa C . Pathophysiology of T follicular helper cells in humans and mice. Nat Immunol. 2015; 16(2):142-52. PMC: 4459756. DOI: 10.1038/ni.3054. View

18.

Alculumbre S, Pattarini L . Purification of Human Dendritic Cell Subsets from Peripheral Blood. Methods Mol Biol. 2016; 1423:153-67. DOI: 10.1007/978-1-4939-3606-9_11. View

19.

Gould H, Sutton B, Beavil A, Beavil R, McCloskey N, Coker H . The biology of IGE and the basis of allergic disease. Annu Rev Immunol. 2002; 21:579-628. DOI: 10.1146/annurev.immunol.21.120601.141103. View

20.

Volpe E, Servant N, Zollinger R, Bogiatzi S, Hupe P, Barillot E . A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol. 2008; 9(6):650-7. DOI: 10.1038/ni.1613. View