Crucial Role of the Interleukin 1 Receptor Family Member T1/ST2 in T Helper Cell Type 2-mediated Lung Mucosal Immune Responses

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1999 Oct 6

PMID 10510079

Citations 132

Authors

A J Coyle

C Lloyd

J Tian

T Nguyen

C Erikkson

L Wang

P Ottoson

P Persson

T Delaney

S Lehar

S Lin

L Poisson

C Meisel

T Kamradt

T Bjerke

D Levinson

J C Gutierrez-Ramos

Affiliations

Soon will be listed here.

Abstract

T1/ST2 is an orphan receptor of unknown function that is expressed on the surface of murine T helper cell type 2 (Th2), but not Th1 effector cells. In vitro blockade of T1/ST2 signaling with an immunoglobulin (Ig) fusion protein suppresses both differentiation to and activation of Th2, but not Th1 effector populations. In a nascent Th2-dominated response, anti-T1/ST2 monoclonal antibody (mAb) inhibited eosinophil infiltration, interleukin 5 secretion, and IgE production. To determine if these effects were mediated by a direct effect on Th2 cells, we next used a murine adoptive transfer model of Th1- and Th2-mediated lung mucosal immune responses. Administration of either T1/ST2 mAb or T1/ST2-Ig abrogated Th2 cytokine production in vivo and the induction of an eosinophilic inflammatory response, but failed to modify Th1-mediated inflammation. Taken together, our data demonstrate an important role of T1/ST2 in Th2-mediated inflammatory responses and suggest that T1/ST2 may prove to be a novel target for the selective suppression of Th2 immune responses.

Citing Articles

ST2L promotes VEGFA-mediated angiogenesis in gastric cancer by activating TRAF6/PI3K/Akt/NF-κB pathway via IL-33.

Zhu Y, Lu Y, Zhu Y, Ren X, Deng Q, Yang M Sci Rep. 2024; 14(1):26393.

PMID: 39488565 PMC: 11531471. DOI: 10.1038/s41598-024-76763-6.

A type 1 immunity-restricted promoter of the IL-33 receptor gene directs antiviral T-cell responses.

Brunner T, Serve S, Marx A, Fadejeva J, Saikali P, Dzamukova M Nat Immunol. 2024; 25(2):256-267.

PMID: 38172258 PMC: 10834369. DOI: 10.1038/s41590-023-01697-6.

A biomarker for bacteremia in pregnant women with acute pyelonephritis: soluble suppressor of tumorigenicity 2 or sST2.

Chatterton C, Romero R, Jung E, Gallo D, Suksai M, Diaz-Primera R J Matern Fetal Neonatal Med. 2023; 36(1):2183470.

PMID: 36997168 PMC: 10352993. DOI: 10.1080/14767058.2023.2183470.

Soluble ST2 as a New Oxidative Stress and Inflammation Marker in Metabolic Syndrome.

Roy I, Jover E, Matilla L, Alvarez V, Fernandez-Celis A, Beunza M Int J Environ Res Public Health. 2023; 20(3).

PMID: 36767947 PMC: 9915842. DOI: 10.3390/ijerph20032579.

Immunotherapy in the Treatment of Allergic Rhinitis in Children.

Alamri R, Aljabri G, Tahlawi R, Aljabri H Cureus. 2023; 14(12):e32464.

PMID: 36644088 PMC: 9834958. DOI: 10.7759/cureus.32464.

References

Klemenz R, Hoffmann S, Werenskiold A . Serum- and oncoprotein-mediated induction of a gene with sequence similarity to the gene encoding carcinoembryonic antigen. Proc Natl Acad Sci U S A. 1989; 86(15):5708-12. PMC: 297699. DOI: 10.1073/pnas.86.15.5708. View

Lohning M, Grogan J, Coyle A, Yazdanbakhsh M, Meisel C, Gutierrez-Ramos J . T1/ST2 expression is enhanced on CD4+ T cells from schistosome egg-induced granulomas: analysis of Th cell cytokine coexpression ex vivo. J Immunol. 1999; 162(7):3882-9. View

Seder R, Germain R, Linsley P, Paul W . CD28-mediated costimulation of interleukin 2 (IL-2) production plays a critical role in T cell priming for IL-4 and interferon gamma production. J Exp Med. 1994; 179(1):299-304. PMC: 2191346. DOI: 10.1084/jem.179.1.299. View

Coyle A, Le Gros G, Bertrand C, Tsuyuki S, Heusser C, Kopf M . Interleukin-4 is required for the induction of lung Th2 mucosal immunity. Am J Respir Cell Mol Biol. 1995; 13(1):54-9. DOI: 10.1165/ajrcmb.13.1.7598937. View

Gachter T, Werenskiold A, Klemenz R . Transcription of the interleukin-1 receptor-related T1 gene is initiated at different promoters in mast cells and fibroblasts. J Biol Chem. 1996; 271(1):124-9. DOI: 10.1074/jbc.271.1.124. View

Parnet P, Garka K, Bonnert T, Dower S, Sims J . IL-1Rrp is a novel receptor-like molecule similar to the type I interleukin-1 receptor and its homologues T1/ST2 and IL-1R AcP. J Biol Chem. 1996; 271(8):3967-70. DOI: 10.1074/jbc.271.8.3967. View

Ho I, Hodge M, Rooney J, Glimcher L . The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell. 1996; 85(7):973-83. DOI: 10.1016/s0092-8674(00)81299-4. View

Zheng W, Flavell R . The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell. 1997; 89(4):587-96. DOI: 10.1016/s0092-8674(00)80240-8. View

Medzhitov R, Preston-Hurlburt P, Janeway Jr C . A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997; 388(6640):394-7. DOI: 10.1038/41131. View

10.

Zhang D, COHN L, Ray P, Bottomly K, Ray A . Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J Biol Chem. 1997; 272(34):21597-603. DOI: 10.1074/jbc.272.34.21597. View

11.

Sallusto F, Mackay C, Lanzavecchia A . Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science. 1997; 277(5334):2005-7. DOI: 10.1126/science.277.5334.2005. View

12.

Hamelmann E, Schwarze J, Takeda K, Oshiba A, Larsen G, Irvin C . Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med. 1997; 156(3 Pt 1):766-75. DOI: 10.1164/ajrccm.156.3.9606031. View

13.

Torigoe K, USHIO S, Okura T, Kobayashi S, Taniai M, Kunikata T . Purification and characterization of the human interleukin-18 receptor. J Biol Chem. 1997; 272(41):25737-42. DOI: 10.1074/jbc.272.41.25737. View

14.

COHN L, Homer R, Marinov A, Rankin J, Bottomly K . Induction of airway mucus production By T helper 2 (Th2) cells: a critical role for interleukin 4 in cell recruitment but not mucus production. J Exp Med. 1997; 186(10):1737-47. PMC: 2199146. DOI: 10.1084/jem.186.10.1737. View

15.

Bonecchi R, Bianchi G, Bordignon P, DAmbrosio D, Lang R, Borsatti A . Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med. 1998; 187(1):129-34. PMC: 2199181. DOI: 10.1084/jem.187.1.129. View

16.

Rock F, Hardiman G, Timans J, Kastelein R, Bazan J . A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci U S A. 1998; 95(2):588-93. PMC: 18464. DOI: 10.1073/pnas.95.2.588. View

17.

Xu D, Chan W, Leung B, Huang F, Wheeler R, Piedrafita D . Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells. J Exp Med. 1998; 187(5):787-94. PMC: 2212173. DOI: 10.1084/jem.187.5.787. View

18.

Lohning M, Stroehmann A, Coyle A, Grogan J, Lin S, Gutierrez-Ramos J . T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function. Proc Natl Acad Sci U S A. 1998; 95(12):6930-5. PMC: 22690. DOI: 10.1073/pnas.95.12.6930. View

19.

Schweitzer A, Sharpe A . Studies using antigen-presenting cells lacking expression of both B7-1 (CD80) and B7-2 (CD86) show distinct requirements for B7 molecules during priming versus restimulation of Th2 but not Th1 cytokine production. J Immunol. 1998; 161(6):2762-71. View

20.

Xu D, Chan W, Leung B, Hunter D, Schulz K, Carter R . Selective expression and functions of interleukin 18 receptor on T helper (Th) type 1 but not Th2 cells. J Exp Med. 1998; 188(8):1485-92. PMC: 2213413. DOI: 10.1084/jem.188.8.1485. View