Pathophysiology in Hypertension: Opposing Roles of Human Adaptive Immunity

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Pathophysiology in Hypertension: Opposing Roles of Human Adaptive Immunity

August 19, 2016 by 2012pharmaceutical

Pathophysiology in Hypertension: Opposing Roles of Human Adaptive Immunity

Reporter: Aviva Lev-Ari, PhD, RN

T regulatory lymphocytes counteract hypertensive effects by suppressing innate and adaptive immune responses and T effector lymphocytes promote differentiation towards pro-inflammatory T helper cells

Dual opposing roles of adaptive immunity in hypertension

Noureddine Idris-Khodja, Muhammad Oneeb Rehman Mian, Pierre Paradis, Ernesto L. Schiffrin

DOI: http://dx.doi.org/10.1093/eurheartj/ehu119 1238-1244 First published online: 30 March 2014

Abstract

Hypertension involves remodelling and inflammation of the arterial wall. Interactions between vascular and inflammatory cells play a critical role in disease initiation and progression. T effector and regulatory lymphocytes, members of the adaptive immune system, play contrasting roles in hypertension. Signals from the central nervous system and the innate immune system antigen-presenting cells activate T effector lymphocytes and promote their differentiation towards pro-inflammatory T helper (T_h) 1 and T_h17 phenotypes. T_h1 and T_h17 effector cells, via production of pro-inflammatory mediators, participate in the low-grade inflammation that leads to blood pressure elevation and end-organ damage. T regulatory lymphocytes, on the other hand, counteract hypertensive effects by suppressing innate and adaptive immune responses. The present review summarizes and discusses the adaptive immune mechanisms that participate in the pathophysiology in hypertension.

Blood pressure
Adaptive immunity
Inflammation
T effector lymphocytes
T regulatory lymphocytes
Cytokines

Conclusion

Experimental and clinical evidence discussed in this review strongly suggests that adaptive immunity, represented by T effector and regulatory lymphocyte subsets, plays a dual role in hypertension (Figure 2). Increased sympathetic outflow as a consequence of stimulation of the CNS by hypertensive stimuli may result in mild blood pressure elevation, causing tissue injury and formation of neoantigens² and/or damage-associated molecular patterns (DAMPs).⁸⁰ Activation of innate APCs by DAMPs, or by pathogen-associated molecular patterns (PAMPs) generated in response to low-grade infection,^80,81 and direct stimulation by CNS, may be the cause of activation of CD4⁺, and perhaps CD8⁺, T effector lymphocytes, and differentiation of CD4⁺ T cells towards pro-inflammatory T_h1/T_h17 phenotypes.⁴¹ T_h1/T_h17 effector lymphocytes contribute to the progression of hypertension by producing pro-inflammatory mediators, including ROS, IFN-γ, TNF-α, and IL-17, to promote low-grade inflammation.^{24,41,42,51,52} T regulatory lymphocytes, on the other hand, counteract hypertensive abnormalities by suppressing innate and adaptive immune responses, perhaps by secreting IL-10.^65–71 As such, circulating levels of Tregs or their immune-suppressive activity may be affected in hypertension.

SOURCE

http://eurheartj.oxfordjournals.org/content/35/19/1238

Idris-Khodja et al. (2014) Dual opposing roles of adaptive immunity in hypertension. European Heart Journal (doi: 10.1093/eurheartj/ehu119)

Figure 1

Differentiation of naïve T lymphocytes into various subsets in a normal immune response. Antigen-presenting cells (dendritic cells and monocyte/macrophages) present antigens on major histocompatibility complex (MHC)-II to naïve T cells (T_h0) in secondary lymphoid tissues, leading to T-cell clonal expansion and differentiation into effector T cells, such as T helper (T_h)1, T_h2, and T_h17 or T regulatory (T_reg) cells according to combined stimulation by different cytokines. T_h effector lymphocytes and Tregs migrate into tissues such as the vasculature, particularly at the level of the adventitia and perivascular fat. The effector lymphocytes (T_h1 and T_h17) cells activate other immune cells and participate in inflammation by producing pro-inflammatory cytokines such as interferon-γ, interleukin (IL)-6, and IL-17. T regulatory lymphocytes suppress innate and adaptive responses via production of anti-inflammatory cytokines IL-10 and transforming growth factor-β. CD, cluster of differentiation; DC, dendritic cell; MΦ, macrophage; NK cell, natural killer cell; T_c, cytotoxic T cell; TCR, T-cell receptor.

IMAGE SOURCE

http://eurheartj.oxfordjournals.org/content/35/19/1238

IMAGE SOURCE

http://eurheartj.oxfordjournals.org/content/35/19/1238

Figure 2

Proposed role of T effector and regulatory lymphocytes in hypertension. Slight elevation in blood pressure (BP) in response to hypertensive stimuli (angiotensin II, aldosterone, endothelin-1, salt and genetic susceptibility) occurs due to increased central signalling, perhaps causing mild tissue injury and formation of damage-associated molecular patterns (DAMPs) and neoantigens. This may lead to activation of innate antigen-presenting cells (APCs) and, subsequently, activation and polarization of naïve CD4⁺ T effector lymphocytes (T_h0) towards pro-inflammatory T helper (T_h)1/T_h17 phenotypes. T_h1/T_h17 may contribute to vascular and kidney damage via production of reactive oxygen species (ROS), interferon (IFN)-γ and interleukin (IL)-17 and lead to maintenance of hypertension and progression of end-organ damage. T regulatory lymphocytes counteract hypertension and associated injury by producing IL-10 or by other mechanisms, and suppression of innate and adaptive immune responses. CD, cluster of differentiation; CNS, central nervous system; MHC-II, major histocompatibility complex-II; PAMPs, pathogen-associated molecular patterns; TCR, T-cell receptor.