Tissue residency and transit of both innate and adaptive immune cells are part of the physiological developmental program of multiple organs. In health, these cells function to remove cellular debris, remodel tissue architecture through growth and development, and surveil against opportunistic and chronic ...
Tissue residency and transit of both innate and adaptive immune cells are part of the physiological developmental program of multiple organs. In health, these cells function to remove cellular debris, remodel tissue architecture through growth and development, and surveil against opportunistic and chronic pathogens. However, these programs breakdown in tissue-specific autoimmune diseases, including in Type 1 Diabetes (T1D), in which the pancreatic insulin-producing beta cells are destroyed by the immune system. Traditionally, islet inflammation (insulitis) has been the histological hallmark of T1D. After careful examination of human pancreas samples collected over the last 50 years, it is now apparent that insulitis is frequently present near T1D onset, but its detection dramatically decreases over time. Moreover, emerging studies now support a generalized pancreatic mass defect and additional abnormalities and cellular infiltration within the acinar tissues surrounding the islets of Langerhans. However, little is known about the phenotype of the infiltrating cells, their antigen specificity, and how they recirculate to lymph nodes, blood and vice-versa. Innate immune cells like macrophages and neutrophils are likely to be present in early stages of the disease, potentially initiating inflammation and regulating lymphocyte entry into the islet. Tissue-resident CD8+ T cells can be found in non-diabetic pancreas but their numbers are increased in recent-onset T1D subjects, and they can persist for years in the tissue. Their role in T1D pathogenesis is currently unknown. These cells typically remain at the site, or in close proximity to sites of infection, and they are rapidly mobilized if a reinfection occurs. Their presence in the pancreas could therefore indicate a role for prior infectious challenges in initiating the disease. There remain a number of knowledge gaps and outstanding questions including the degree to which the accumulation of these cells is antigen-dependent, their motility and functional state(s), and if they are directly required for disease pathogenesis or rather constitute a bystander signature of inflammation.
With this Research Topic, we welcome the submission of original research manuscripts, reviews/mini-reviews, perspective and opinion articles on any relevant subjects related to homing and footprints of immune cells in T1D, including but not limited to the following themes:
o Tissue-resident antigen-presenting cells.
o Tissue-resident T cells – specificity and function.
o Soluble factors that could attract immune cells to the pancreas, including cytokines and chemokines.
o Role of the tissue microenvironment in the immune infiltration in the pancreas, e.g. nutrients, metabolites, oxygen, hormones, cellular signaling etc., and the cross-talk between immune cells and beta cells.
o The role of the innate immune system in tissue development, remodeling, and repair following damage.
o Impact of altered innervation, vascularization and extracellular matrix in innate and adaptive immune regulation.
o Immune cell infiltration in the context of infection.
o Cellular transit from the gastrointestinal tract to pancreatic lymph nodes and the pancreas.
Potential strategies to modulate the homing of immune cells to the pancreas.
type 1 diabetes, tissue residence, immune cells, trafficking, cytokines, chemokines
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