Membrane bound IL-15 is increased on CD14 monocytes in early stages of MS
Adi Vaknin-Dembinsky1, Steven D Brass, Steven Brass
1Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical, School, Boston Massachusetts 02115, United States.
Abstract:
IL-15 is a pro-inflammatory cytokine whose three-dimensional structure is similar to that of IL-2. IL-2 and IL-15 have similar as well as distinct biological functions. An active form of IL-15 that is membrane bound has also been described. Furthermore, IL-15 is known to play a role in autoimmune diseases. We thus investigated the expression of membrane bound IL-15 on monocytes (CD14+ cells) and studied its effect on T cell activation in MS patients. We found that unstimulated CD14+ cells from relapsing remitting MS patients had increased membrane bound IL-15. Those with high surface levels of IL-15 on monocytes were in the early stages of the disease. In addition, we found that T cells of MS patients had enhanced responsiveness to IL-15 and there was increased expression of IL-15 receptor on CD4+ T cells. Thus, IL-15 may be an important cytokine that drives Th1 responses early in the course of the disease and could serve as a target for immunotherapy and as an early marker in the immunologic staging of MS.
Insights
Increased membrane-bound Interleukin-15 (IL-15) on monocytes in early multiple sclerosis (MS) patients correlates with enhanced T cell activation, suggesting IL-15 as an early disease marker and therapeutic target.
Area of Science:
- Immunology
- Neuroimmunology
Background:
- Interleukin-15 (IL-15) is a pro-inflammatory cytokine with structural and functional similarities to IL-2.
- IL-15 plays a role in autoimmune diseases, and a membrane-bound active form has been identified.
Purpose of the Study:
- To investigate the expression of membrane-bound IL-15 on monocytes (CD14+ cells).
- To study the effect of membrane-bound IL-15 on T cell activation in patients with multiple sclerosis (MS).
Main Methods:
- Flow cytometry was used to analyze membrane-bound IL-15 expression on CD14+ monocytes.
- T cell activation and IL-15 receptor expression on CD4+ T cells were assessed in MS patients.
Main Results:
- Unstimulated CD14+ cells from relapsing-remitting MS patients showed increased membrane-bound IL-15.
- Higher surface IL-15 levels on monocytes were associated with early disease stages.
- MS patients exhibited enhanced T cell responsiveness to IL-15 and increased IL-15 receptor expression on CD4+ T cells.
Conclusions:
- Membrane-bound IL-15 may drive T-helper 1 (Th1) responses early in MS pathogenesis.
- IL-15 could serve as a potential biomarker for early immunologic staging of MS.
- IL-15 represents a potential target for MS immunotherapy.
