Effect of tyrosine hydroxylase overexpression in lymphocytes on the differentiation and function of T helper cells

Huang, Hua; Zuo, Cong; Xiao, Chen; Peng, Yu‐Ping; Qiu, Yihua

doi:10.3892/ijmm.2016.2639

Cited by 11 publications

(9 citation statements)

References 40 publications

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“…Some authors have proposed that also T cells express TH 64,65 , and similar mechanisms as described for B cells in the present report, might also be valid for T cell or other TH expressing immune cells. However, there are also immune cells, like macrophages, that do express transporters for catecholamines, but are not capable of synthesizing catecholamines on their own 66 .…”

Section: Discussionsupporting

confidence: 86%

TLR9-activated B cells improve their regulatory function by endogenously produced catecholamines

Honke

Lowin

Opgenoorth

et al. 2020

Preprint

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The sympathetic nervous system (SNS) contributes to immune balance by promoting antiinflammatory B cells. However, whether B cells possess a self-regulating mechanism by which they modulate regulatory B cell (Breg) function is not well understood. In this study, we investigated the ability of B cells to synthesize catecholamines upon stimulation with different B cell activators. We found, that expression of the enzymes required to generate catecholamines, is upregulated by TLR9. TLR-9-specific expression of tyrosine hydroxylase (TH) correlated with upregulation of adrenergic receptors, enhanced IL-10 production, and with an overexpression of the co-inhibitory ligands PD-L1 and FasL. Moreover, concomitant stimulation of ß1-3-adrenergic receptors together with a BCR/TLR9 stimulus enhances the anti-inflammatory potential of Bregs to suppress CD4 T cells, a crucial population in the pathogenesis of autoimmune diseases, like rheumatoid arthritis. In conclusion, our data show that B cells possess autonomous mechanisms to modulate their regulatory function. These findings help to better understand the function of Bregs in autoimmune diseases and the interplay of sympathetic nervous system and B cell function.3 Introduction:

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Section: Discussionsupporting

confidence: 86%

TLR9-activated B cells improve their regulatory function by endogenously produced catecholamines

Honke

Lowin

Opgenoorth

et al. 2020

Preprint

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“…Our recent study demonstrated reduced noradrenaline concentration in dLNs from DA rats on the 7th day postimmunization (59). However, noradrenaline content was increased in dLN cells constituting, most likely, a compensatory mechanism (42,127,128). Early studies in active (129) and adoptively transferred (130) Lewis rat EAE showed more severe disease in adult rats subjected to 6-hydroxydopamine-induced sympathectomy at birth.…”

Section: Animal Datamentioning

confidence: 88%

Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis

et al. 2020

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The role of stress effector systems in the initiation and progression of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the most commonly used experimental model of MS, has strongly been suggested. To corroborate this notion, alterations in activity of the sympathoadrenal and sympathoneural axes of sympathoadrenal system (a major communication pathway between the central nervous system and the immune system), mirrored in altered release of their end-point mediators (adrenaline and noradrenaline, respectively), are shown to precede (in MS) and/or occur during development of MS and EAE in response to immune cell activation (in early phase of disease) and disease-related damage of sympathoadrenal system neurons and their projections (in late phase of disease). To add to the complexity, innate immunity cells and T-lymphocytes synthesize noradrenaline that may be implicated in a local autocrine/paracrine self-amplifying feed-forward loop to enhance myeloid-cell synthesis of proinflammatory cytokines and inflammatory injury. Furthermore, experimental manipulations targeting noradrenaline/adrenaline action are shown to influence clinical outcome of EAE, in a disease phase-specific manner. This is partly related to the fact that virtually all types of cells involved in the instigation and progression of autoimmune inflammation and target tissue damage in EAE/MS express functional adrenoceptors. Although catecholamines exert majority of immunomodulatory effects through β 2-adrenoceptor, a role for α-adrenoceptors in EAE pathogenesis has also been indicated. In this review, we summarize all aforementioned aspects of immunopathogenetic action of catecholamines in EAE/MS as possibly important for designing new strategies targeting their action to prevent/mitigate autoimmune neuroinflammation and tissue damage.

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“…TH is the rate-limiting enzyme in the synthesis of catecholamines ( 67 ). Huang et al reported that overexpressed TH promotes the differentiation of CD4 + T cells to Th2 cells ( 68 ), which suggested a possible role of the TH gene in regulating immune cell function. Notably, we found that TH was consistently negatively correlated with MHC molecules at the gene level, highlighting the importance of the TH gene in antigen presentation.…”

Section: Discussionmentioning

confidence: 99%

Tumor Immunometabolism Characterization in Ovarian Cancer With Prognostic and Therapeutic Implications

et al. 2021

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Metabolic dysregulation in the tumor microenvironment has significant impact on immune infiltration and immune responses. However, interaction between immunity and metabolism in the ovarian microenvironment requires further exploration. We constructed an immunometabolism gene set and ovarian cancer cohort from The Cancer Genome Atlas (TCGA) and classified these into three immunometabolism subtypes. We explored the relationships between immune infiltration and metabolic reprogramming. Additionally, we built risk score and nomogram as prognostic signatures. Three distinctive immunometabolism subtypes were identified with therapeutic and prognostic implications. Subtype 1, the “immune suppressive-glycan metabolism subtype,” featured high levels of immunosuppressive cell infiltration and glycan metabolism activation; Subtype 2, the “immune inflamed-amino acid metabolism subtype,” showed abundant adaptive immune cell infiltration and amino acid metabolism activation; Subtype 3, the “immune desert-endocrine subtype,” was characterized by low immune cell infiltration and upregulation of hormone biosynthesis. Furthermore, we found that epinephrine biosynthesis displayed a significantly negative correlation with MHC molecules, which may result in defective antigen presentation. We proposed immunometabolism subtypes with prognostic implications and provided new perspectives for the ovarian cancer microenvironment.

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Effect of tyrosine hydroxylase overexpression in lymphocytes on the differentiation and function of T helper cells

Cited by 11 publications

References 40 publications

TLR9-activated B cells improve their regulatory function by endogenously produced catecholamines

TLR9-activated B cells improve their regulatory function by endogenously produced catecholamines

Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis

Tumor Immunometabolism Characterization in Ovarian Cancer With Prognostic and Therapeutic Implications

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