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Review
. 2019 Jan 22:10:11.
doi: 10.3389/fimmu.2019.00011. eCollection 2019.

Dendritic Cell Subsets and Effector Function in Idiopathic and Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Denise van Uden  1 , Karin Boomars  1 , Mirjam Kool  1
Affiliations
Review

Dendritic Cell Subsets and Effector Function in Idiopathic and Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Denise van Uden et al. Front Immunol. .

Abstract

Pulmonary arterial hypertension (PAH) is a cardiopulmonary disease characterized by an incurable condition of the pulmonary vasculature, leading to increased pulmonary vascular resistance, elevated pulmonary arterial pressure resulting in progressive right ventricular failure and ultimately death. PAH has different underlying causes. In approximately 30-40% of the patients no underlying risk factor or cause can be found, so-called idiopathic PAH (IPAH). Patients with an autoimmune connective tissue disease (CTD) can develop PAH [CTD-associated PAH (CTD-PAH)], suggesting a prominent role of immune cell activation in PAH pathophysiology. This is further supported by the presence of tertiary lymphoid organs (TLOs) near pulmonary blood vessels in IPAH and CTD-PAH. TLOs consist of myeloid cells, like monocytes and dendritic cells (DCs), T-cells, and B-cells. Next to their T-cell activating function, DCs are crucial for the preservation of TLOs. Multiple DC subsets can be found in steady state, such as conventional DCs (cDCs), including type 1 cDCs (cDC1s), and type 2 cDCs (cDC2s), AXL+Siglec6+ DCs (AS-DCs), and plasmacytoid DCs (pDCs). Under inflammatory conditions monocytes can differentiate into monocyte-derived-DCs (mo-DCs). DC subset distribution and activation status play an important role in the pathobiology of autoimmune diseases and most likely in the development of IPAH and CTD-PAH. DCs can contribute to pathology by activating T-cells (production of pro-inflammatory cytokines) and B-cells (pathogenic antibody secretion). In this review we therefore describe the latest knowledge about DC subset distribution, activation status, and effector functions, and polymorphisms involved in DC function in IPAH and CTD-PAH to gain a better understanding of PAH pathology.

Keywords: autoimmune disease; connective tissue disease; dendritic cell; dendritic cell effector function; dendritic cell subsets; idiopathic pulmonary arterial hypertension; pulmonary arterial hypertension.

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Figures

Figure 1
Figure 1
cDC and monocyte migration toward lung TLOs. (A) cDCs and monocytes are decreased in circulation of IPAH patients due to migration to the lungs in which cDCs and monocytes are increased. (B) In the lung they can add to the development of TLOs surrounding PAs. (C) TLOs consist, besides DCs, of different immune cells such as T-cells, B-cells, macrophages, and granulocytes.
Figure 2
Figure 2
Involvement of DCs and monocyte in lungs of IPAH and CTD-PAH patients. (A) pDCs are increased in lungs and might play a role in IPAH and CTD-PAH pathology by producing higher levels of CXCL4 and CXCL10 that is induced by IFNs. (B) cDC display higher levels of CD83 and have an enhanced cytokine production e.g., IL-6. cDCs are increased in lungs of PAH patients and can directly lead to PA remodeling or indirectly by production of CXCL13 and CCL20. CXCL13 leads to migration of B-cells toward the lungs, B-cells will produce pathogenic antibodies after interaction with Tfh cells, leading to remodeling of PAs. CCL20 attracts T-cells such as Tregs and Th17 cells leading to an increase in Th17 cells in the lung resulting in a Th17/Treg disbalance and by IL-17 production contributes to PA remodeling. (C) Monocytes are increased in the lung and produce CCL2 and CCL5 which might lead to attraction of other monocytes. Monocytes might differentiate in macrophages or mo-DCs. Mo-DCs induce Th17 cells adding to PA remodeling.
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References

    1. Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. . 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. (2016) 37:67–119. 10.1093/eurheartj/ehv317 - DOI - PubMed
    1. Humbert M, Montani D, Perros F, Dorfmüller P, Adnot S, Eddahibi S. Endothelial cell dysfunction and cross talk between endothelium and smooth muscle cells in pulmonary arterial hypertension. Vascul Pharmacol. (2008) 49:113–8. 10.1016/j.vph.2008.06.003 - DOI - PubMed
    1. McGoon MD, Miller DP. REVEAL: a contemporary US pulmonary arterial hypertension registry. Eur Respir Rev. (2012) 21:8–18. 10.1183/09059180.00008211 - DOI - PMC - PubMed
    1. Dhala A. Pulmonary arterial hypertension in systemic lupus erythematosus: current status and future direction. Clin Dev Immunol. (2012) 2012:854941. 10.1155/2012/854941 - DOI - PMC - PubMed
    1. Tselios K, Gladman DD, Urowitz MB. Systemic lupus erythematosus and pulmonary arterial hypertension: links, risks, and management strategies. Open Access Rheumatol. (2017) 9:1–9. 10.2147/OARRR.S123549 - DOI - PMC - PubMed

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