Next Article in Journal / Special Issue
IL-21 in Homeostasis of Resident Memory and Exhausted CD8 T Cells during Persistent Infection
Previous Article in Journal
Sudachinoid- and Ichangensin-Type Limonoids from Citrus junos Downregulate Pro-Inflammatory Cytokines
Previous Article in Special Issue
Combination of High Dose Hypofractionated Radiotherapy with Anti-PD1 Single Dose Immunotherapy Leads to a Th1 Immune Activation Resulting in a Complete Clinical Response in a Melanoma Patient
Article

Semaphorin4A-Plexin D1 Axis Induces Th2 and Th17 While Represses Th1 Skewing in an Autocrine Manner

1
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, University of Utrecht, 3508 GA Utrecht, The Netherlands
2
Center for Translational Immunology, University Medical Center Utrecht, University of Utrecht, 3508 GA Utrecht, The Netherlands
3
Rheumatology & Immuno-mediated Diseases Research Group (IRIDIS), Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36312 Vigo, Spain
4
Rheumatology Department, University Hospital Complex of Vigo, 36312 Vigo, Spain
*
Author to whom correspondence should be addressed.
These authors equally contributed to this work.
Int. J. Mol. Sci. 2020, 21(18), 6965; https://doi.org/10.3390/ijms21186965
Received: 31 August 2020 / Revised: 17 September 2020 / Accepted: 19 September 2020 / Published: 22 September 2020
(This article belongs to the Special Issue Recent Advances in T Cell Immunity)
Semaphorin (Sema)4A is a transmembrane glycoprotein that is elevated in several autoimmune diseases such as systemic sclerosis, rheumatoid arthritis and multiple sclerosis. Sema4A has a key role in the regulation of Thelper Th1 and Th2 differentiation and we recently demonstrated that CD4+ T cell activation induces the expression of Sema4A. However, the autocrine role of Sema4A on Th cell differentiation remains unknown. Naïve Th cells from healthy controls were cell sorted and differentiated into Th1, Th2 and Th17 in the presence or absence of a neutralizing antibody against the Sema4A receptor PlexinD1. Gene expression was determined by quantitative PCR and protein expression by ELISA and flow cytometry. We found that the expression of Sema4A is induced during Th1, Th2 and Th17 differentiation. PlexinD1 neutralization induced the differentiation of Th1 cells, while reduced the Th2 and Th17 skewing. These effects were associated with an upregulation of the transcription factor T-bet by Th1 cells, and to downregulation of GATA3 and RORγt in Th2 cells and Th17 cells, respectively. Finally, PlexinD1 neutralization regulates the systemic sclerosis patients serum-induced cytokine production by CD4+ T cells. Therefore, the autocrine Sema4A-PlexinD1 signaling acts as a negative regulator of Th1 skewing but is a key mediator on Th2 and Th17 differentiation, suggesting that dysregulation of this axis might be implicated in the pathogenesis of CD4+ T cell-mediated diseases. View Full-Text
Keywords: semaphorin4A; plexinD1; CD4+ T cell differentiation; T helper cells; systemic sclerosis semaphorin4A; plexinD1; CD4+ T cell differentiation; T helper cells; systemic sclerosis
Show Figures

Graphical abstract

MDPI and ACS Style

Carvalheiro, T.; Rafael-Vidal, C.; Malvar-Fernandez, B.; Lopes, A.P.; Pego-Reigosa, J.M.; Radstake, T.R.D.J.; Garcia, S. Semaphorin4A-Plexin D1 Axis Induces Th2 and Th17 While Represses Th1 Skewing in an Autocrine Manner. Int. J. Mol. Sci. 2020, 21, 6965. https://doi.org/10.3390/ijms21186965

AMA Style

Carvalheiro T, Rafael-Vidal C, Malvar-Fernandez B, Lopes AP, Pego-Reigosa JM, Radstake TRDJ, Garcia S. Semaphorin4A-Plexin D1 Axis Induces Th2 and Th17 While Represses Th1 Skewing in an Autocrine Manner. International Journal of Molecular Sciences. 2020; 21(18):6965. https://doi.org/10.3390/ijms21186965

Chicago/Turabian Style

Carvalheiro, Tiago; Rafael-Vidal, Carlos; Malvar-Fernandez, Beatriz; Lopes, Ana P.; Pego-Reigosa, Jose M.; Radstake, Timothy R.D.J.; Garcia, Samuel. 2020. "Semaphorin4A-Plexin D1 Axis Induces Th2 and Th17 While Represses Th1 Skewing in an Autocrine Manner" Int. J. Mol. Sci. 21, no. 18: 6965. https://doi.org/10.3390/ijms21186965

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop