Background/Purpose: The sympathetic nervous system (SNS) plays an important role in course and development of autoimmune diseases like arthritis. In type II collagen- induced arthritis (CIA), early activation of the SNS is proinflammatory, but the SNS is anti-inflammatory in later stages of disease. Early sympathectomy (SYX) prior to immunization ameliorates disease severity, but beneficial mechanisms of early SYX are not completely understood. The aim of this study was to determine how the SNS influences energy expenditure in lymph nodes / spleen and, in parallel, egress of lymphocytes from draining lymph nodes / spleen of control and arthritic animals.

Methods: A new technique termed “spatial energy expenditure configuration (SEEC)” was developed to demonstrate bodily areas of high energy demand. SEEC is based on removal of tissue during the course of arthritis in DBA/1 mice, and subsequent determination of oxygen consumption in vitro as a measure of local energy expenditure (immune cell activation). SEEC was applied to healthy control animals, arthritic animals, and animals that underwent early SYX. We evaluated homing behaviour of labelled donor splenocytes, expression of CCR7 on lymphocytes by flow cytometry, concentration of CCL21 in lymphocyte cell culture supernatants, and levels of sphingosine-1-phosphate (S1P) in serum of arthritic, sympathectomized arthritic, and control animals.

Results: In draining lymph nodes and spleens of arthritic mice, we observed a marked increase in oxygen consumption and organ weight during the course of arthritis. Although early SYX ameliorated later CIA, early SYX increased energy consumption and cell numbers in arthritic but also in control lymph nodes. This was interpreted as a probable sign of lymphocyte retention in lymphoid organs in healthy and arthritic animals. Splenocyte migration to the spleen was enhanced in early SYX compared to control mice. After early SYX, we observed an elevated expression of CCR7 on lymph node cells and a higher level of CCL21 in lymphocyte cell culture supernatants. This probably contributes to retention of T cells and dendritic cells within lymph nodes. Egress of lymphocytes requires an S1P gradient, low in the lymph node parenchyma and high at the exit site in the vascular lumen. The measurement of S1P in mouse serum revealed a significant higher concentration in CIA animals when compared to controls. Importantly, early SYX decreased S1P concentration in arthritic animals to control levels.

Conclusion: By using the SEEC technique, we identified draining lymph nodes as target organs of the sympathetic nervous system. SYX-induced disease amelioration is probably exerted by sequestration of lymphocytes in secondary lymphoid organs. This might prevent recirculation of immune cells to peripheral sites of inflammation.

 

 

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/early-sympathectomy-inhibits-egress-of-lymphocytes-in-control-and-arthritic-animals-and-ameliorates-arthritic-disease/