SIGIRR and TNFAIP3 Are Differentially Expressed in Both PBMC and TNF-α Secreting Cells of Patients With Major Depressive Disorder

Overview

Journal Front Psychiatry

Specialty Psychiatry

Date 2021 Aug 16

PMID 34393859

Citations 1

Authors

Chin-Chuen Lin

Tiao-Lai Huang

Affiliations

Soon will be listed here.

Abstract

Major depressive disorder (MDD) is associated with the activation of the immune/inflammatory system. TNF-α is associated with MDD and poor treatment response. Toll-like receptors (TLR) are responsible in innate immune response, and is associated with MDD and antidepressant response. Some negative regulators of TLR pathway such as SOCS1, TOLLIP, SIGIRR, TNFAIP3, and MyD88s, are reported to be differentially expressed in the peripheral blood samples of patients of MDD. We recruited patients with MDD and healthy controls, collect their demographic data, and measured their mRNA levels of negative TLR regulators, using peripheral blood mononuclear cells (PBMC) and isolated TNF-α secreting cells. Clinical symptoms were evaluated using Halmiton Depression Rating Scale (Ham-D). Some patients were evaluated again after 4 weeks of antidepressant treatment. Forty-seven patients with MDD and 52 healthy controls were recruited. Between the PBMC samples of 37 MDD patients and 42 controls, mRNA levels of SOCS1, SIGIRR, TNFAIP3, and MyD88s were significantly different. Between TNF-α secreting cells of 10 MDD patients and 10 controls, mRNA levels of SIGIRR and TNFAIP3 were significantly different. Change of Ham-D score only correlated significantly with TOLLIP mRNA level after treatment. SIGIRR and TNFAIP3, two negative regulators of TLR immune response pathways, were differentially expressed in both PBMC and TNF-α secreting cells of patients with MDD as compared to healthy controls. The negative regulations of innate immune response could contribute to the underlying mechanism of MDD.

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References

Barzman D, Eliassen J, McNamara R, Abonia P, Mossman D, Durling M . Correlations of inflammatory gene pathways, corticolimbic functional activities, and aggression in pediatric bipolar disorder: a preliminary study. Psychiatry Res. 2014; 224(2):107-11. PMC: 4197049. DOI: 10.1016/j.pscychresns.2014.07.009. View

OBrien S, Scully P, Fitzgerald P, Scott L, Dinan T . Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy. J Psychiatr Res. 2006; 41(3-4):326-31. DOI: 10.1016/j.jpsychires.2006.05.013. View

Kinjyo I, Hanada T, Inagaki-Ohara K, Mori H, Aki D, Ohishi M . SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. Immunity. 2002; 17(5):583-91. DOI: 10.1016/s1074-7613(02)00446-6. View

Takeuchi O, Akira S . Pattern recognition receptors and inflammation. Cell. 2010; 140(6):805-20. DOI: 10.1016/j.cell.2010.01.022. View

Hung Y, Kang H, Huang K, Huang T . Association between toll-like receptors expression and major depressive disorder. Psychiatry Res. 2014; 220(1-2):283-6. DOI: 10.1016/j.psychres.2014.07.074. View

Keshavarzi A, Eftekharian M, Komaki A, Omrani M, Kholghi Oskooei V, Taheri M . Sexual dimorphism in up-regulation of suppressors of cytokine signaling genes in patients with bipolar disorder. BMC Psychiatry. 2019; 19(1):402. PMC: 6915962. DOI: 10.1186/s12888-019-2396-9. View

Seidel A, Arolt V, Hunstiger M, Rink L, Behnisch A, Kirchner H . Cytokine production and serum proteins in depression. Scand J Immunol. 1995; 41(6):534-8. DOI: 10.1111/j.1365-3083.1995.tb03604.x. View

Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim E . A meta-analysis of cytokines in major depression. Biol Psychiatry. 2009; 67(5):446-57. DOI: 10.1016/j.biopsych.2009.09.033. View

Hung Y, Lin C, Kang H, Huang T . TNFAIP3, a negative regulator of the TLR signaling pathway, is a potential predictive biomarker of response to antidepressant treatment in major depressive disorder. Brain Behav Immun. 2016; 59:265-272. DOI: 10.1016/j.bbi.2016.09.014. View

10.

Maes M, Bosmans E, Suy E, Vandervorst C, Dejonckheere C, Raus J . Depression-related disturbances in mitogen-induced lymphocyte responses and interleukin-1 beta and soluble interleukin-2 receptor production. Acta Psychiatr Scand. 1991; 84(4):379-86. DOI: 10.1111/j.1600-0447.1991.tb03163.x. View

11.

Nakagawa R, Naka T, Tsutsui H, Fujimoto M, Kimura A, Abe T . SOCS-1 participates in negative regulation of LPS responses. Immunity. 2002; 17(5):677-87. DOI: 10.1016/s1074-7613(02)00449-1. View

12.

Hung Y . Antidepressants Improve Negative Regulation of Toll-Like Receptor Signaling in Monocytes from Patients with Major Depression. Neuroimmunomodulation. 2018; 25(1):42-48. DOI: 10.1159/000489562. View

13.

Chen R, Huang T, Huang K, Hung Y . TNFAIP3 mRNA Level Is Associated with Psychological Anxiety in Major Depressive Disorder. Neuroimmunomodulation. 2018; 24(4-5):271-275. DOI: 10.1159/000486860. View

14.

Maes M, DeLange J, Ranjan R, Meltzer H, Desnyder R, Cooremans W . Acute phase proteins in schizophrenia, mania and major depression: modulation by psychotropic drugs. Psychiatry Res. 1997; 66(1):1-11. DOI: 10.1016/s0165-1781(96)02915-0. View

15.

Wu M, Huang T, Huang K, Huang Y, Hung Y . Association between toll-like receptor 4 expression and symptoms of major depressive disorder. Neuropsychiatr Dis Treat. 2015; 11:1853-7. PMC: 4525784. DOI: 10.2147/NDT.S88430. View

16.

Hamilton M . Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol. 1967; 6(4):278-96. DOI: 10.1111/j.2044-8260.1967.tb00530.x. View

17.

Padmos R, Hillegers M, Knijff E, Vonk R, Bouvy A, Staal F . A discriminating messenger RNA signature for bipolar disorder formed by an aberrant expression of inflammatory genes in monocytes. Arch Gen Psychiatry. 2008; 65(4):395-407. DOI: 10.1001/archpsyc.65.4.395. View

18.

Sutcigil L, Oktenli C, Musabak U, Bozkurt A, Cansever A, Uzun O . Pro- and anti-inflammatory cytokine balance in major depression: effect of sertraline therapy. Clin Dev Immunol. 2008; 2007:76396. PMC: 2248234. DOI: 10.1155/2007/76396. View

19.

Song C, Dinan T, Leonard B . Changes in immunoglobulin, complement and acute phase protein levels in the depressed patients and normal controls. J Affect Disord. 1994; 30(4):283-8. DOI: 10.1016/0165-0327(94)90135-x. View

20.

Huang K, Wu M, Hung Y . Elevated TNIP3 mRNA Expression in TNF-α-Secreting Cells from Patients with Major Depressive Disorder. Neuroimmunomodulation. 2019; 26(3):153-158. DOI: 10.1159/000501083. View