Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Psoriasis is a common T-cell driven inflammatory skin disorder that is featured by immune cell infiltration, and vasculopathy of both blood and lymphatic vasculature. Psoriatic arthritis (PsA) is a destructive joint disease that occurs in up to 30% of psoriasis patients, but how the disease progresses from only skin inflammation to also synovial membrane involvement of the joints and entheses is unclear. The T helper 17 (Th17) subpopulation has been put forward as the main driver of the disease manifestations in psoriasis and PsA. Recently, our group showed that lymphatic endothelial cells (LEC) lining the interior surface of the lymphatic vasculature, have the capacity to suppress Th17 differentiation and alter the chemokine receptor profile that controls their specific tissue homing. We hypothesize that the LECs in the skin of PsA patients are dysregulated and allow pathogenic Th17 cells to migrate to extracutaneous sites. To get a better understanding of how these regulatory mechanisms affect Th17 migration from skin to synovial joints in PsA, we investigated LEC derived from different sources, and compared LEC with another disease-relevant stromal cells.
Human dermal LEC and dermal fibroblasts (DF) were cell-sorted from skin discarded from healthy individuals undergoing elective skin surgery. Also, LECs were cell-sorted from human lymph nodes derived from patients undergoing vascular surgery without a medical history of chronic inflammatory disorders. We determined the expression of immunomodulatory and co-stimulatory molecules across LEC populations in skin and lymph node, and in DF using flow cytometry and real-time quantitative PCR (qPCR). Subsequently, we assessed the inflammatory responses of dermal LEC and DF by qPCR during a 24 h culture with the cytokines IL-17A, IL-22, TNFα, and IL-1β.
Flow cytometric analysis demonstrated that both lymph node LEC and dermal LEC, but not DF, expressed the MHC class II molecule HLA-DR. In line, qPCR analysis revealed that both lymph node LEC and dermal LEC, but not DF, expressed fundamental immunomodulatory molecules that affect T-cell activation and polarization including programmed death-ligand 1 and 2 (PD-L1/2), galectin 1,3 and 9, glucocorticoid-induced TNFR-related ligand (GITRL), OX40 ligand, and inducible T Cell Costimulator Ligand (ICOS-L). Secondly, a 24 h culture with IL-17A, IL-22 and TNFα, strongly induced ICOS-L and the chemokine ligand 20 (CCL20) in dermal LEC, whereas DF showed no effect upon cytokine stimulation.
We found that human LEC populations in both skin and lymph nodes, as compared to DF, are endowed with immunomodulatory properties underscoring the essential role for LECs in shaping peripheral T-cell responses. Under inflammatory conditions, particularly dermal LECs, but not DF, seem to be important in regulating T-cell activation and recruitment of CCR6-expressing T-cell subpopulations responding to CCL-20. Further studies on LEC populations that originate from
To cite this abstract in AMA style:den Braanker H, Otten-Mus A, Asmawidjaja P, Davelaar N, de Smet AAEA, Akkersdijk GP, Fioole B, Jaquet JB, Hofman A, Schuitema OP, Tas SW, Mebius R, Lubberts E, Kok MR, Bisoendial RJ. Elucidating the Role of the Lymphatic System in the Pathogenesis of Psoriasis and Psoriatic Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/elucidating-the-role-of-the-lymphatic-system-in-the-pathogenesis-of-psoriasis-and-psoriatic-arthritis/. Accessed May 25, 2022.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/elucidating-the-role-of-the-lymphatic-system-in-the-pathogenesis-of-psoriasis-and-psoriatic-arthritis/