Lymphocytes within lymphoid tissues are regulated by a vascular-stromal compartment comprised of blood vessels, lymphatic sinuses, and non-vascular mesenchymal reticular cells, and understanding the functions and regulation of this compartment can have implications for better understanding and treating lymphoproliferative and autoimmune diseases. We have recently shown that fibroblastic reticular cells (FRCs) are in distinct functional states at homeostasis and in inflamed lymph nodes. Our long-term goal is to understand other functional features of the vascular-stromal compartment in inflamed nodes, how these features contribute to regulating immune responses, and how these features in inflamed nodes are induced. Here, we show that FRCs upregulate CCL2 during a phase of the immune response that corresponds to plasma cell accumulation. FRCs express CCL2 at high levels in the vascular-rich medulla and vascular-rich regions of the T zone, which are also the sites of plasma cell localization. We show that CCL2 limits plasma cell survival and that vascular permeability may play a role in inducing the FRC functional phenotype in these vascular-rich regions. We propose to test the hypothesis that, during this phase of the immune response, features of vascular-rich microenvironments regulate plasma cell function and vascular activity regulates FRC functional phenotype in these areas.
Our aims are 1) to understand how CCL2 regulates plasma cell survival and 2) to understand how vascular activity contributes to modulating FRC functional phenotype. The results from this proposal will provide new insights into lymphoid tissue vascular-stromal function and regulation, plasma cell regulation, and a potential link between cardiovascular health and the immune system. This link is especially relevant for autoimmune diseases such as lupus that are characterized both by vascular dysfunction and immune system dysfunction marked in part by plasma cell accumulation
Lymph nodes are sites of immune responses in health and disease. Lymph node fibroblasts can regulate the activity of the immune cells and here we ask how the fibroblasts regulate immune cells and how they are in turn regulated by blood vessel permeability. Understanding how lymph nodes function as a tissue will help us understand how to control pathologic immune responses in autoimmune diseases such as lupus.
|Shipman, William D; Chyou, Susan; Ramanathan, Anusha et al. (2018) A protective Langerhans cell-keratinocyte axis that is dysfunctional in photosensitivity. Sci Transl Med 10:|
|Shipman, William D; Dasoveanu, Dragos C; Lu, Theresa T (2017) Tertiary lymphoid organs in systemic autoimmune diseases: pathogenic or protective? F1000Res 6:196|
|Dasoveanu, Dragos C; Shipman, William D; Chia, Jennifer J et al. (2016) Regulation of Lymph Node Vascular-Stromal Compartment by Dendritic Cells. Trends Immunol 37:764-777|
|Chia, Jennifer J; Zhu, Tong; Chyou, Susan et al. (2016) Dendritic cells maintain dermal adipose-derived stromal cells in skin fibrosis. J Clin Invest 126:4331-4345|
|Chia, Jennifer J; Lu, Theresa T (2015) Update on macrophages and innate immunity in scleroderma. Curr Opin Rheumatol 27:530-6|
|Kumar, Varsha; Dasoveanu, Dragos C; Chyou, Susan et al. (2015) A dendritic-cell-stromal axis maintains immune responses in lymph nodes. Immunity 42:719-30|
|Benahmed, Fairouz; Chyou, Susan; Dasoveanu, Dragos et al. (2014) Multiple CD11c+ cells collaboratively express IL-1? to modulate stromal vascular endothelial growth factor and lymph node vascular-stromal growth. J Immunol 192:4153-63|
|Kumar, Varsha; Chyou, Susan; Stein, Jens V et al. (2012) Optical projection tomography reveals dynamics of HEV growth after immunization with protein plus CFA and features shared with HEVs in acute autoinflammatory lymphadenopathy. Front Immunol 3:282|
|Lu, Theresa T; Kim, Hajeong; Ma, Xiaojing (2012) IL-17, a new kid on the block of tertiary lymphoid organs. Cell Mol Immunol 9:3-4|
|Lu, Theresa T (2012) Dendritic cells: novel players in fibrosis and scleroderma. Curr Rheumatol Rep 14:30-8|
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