Th17 Cells and Lymphotoxin Promote Tertiary Lymphoid Tissues Formation and Neuroinflammation

Th17 Cells and Lymphotoxin Promote Tertiary Lymphoid Tissues Formation and Neuroinflammation

According to a recent study published in Immunity, T helper (Th)17 cells initiate tertiary lymphoid tissues (TLTs) development in the meninges and propagate brain neuroinflammation.

Tertiary lymphoid tissues or tertiary lymphoid organs (TLOs) represent accumulations of lymphoid cells at ectopic sites (in contrast to most lymphoid tissues developing before birth) usually triggered by chronic inflammation.

The present-day view is that TLOs are the result of non-resolving diseases or conditions such as chronic microbial infection, graft rejection, cancer and autoimmune diseases.

In the Immunity study Natalia Pikor and colleagues, as part of an international team from Canada, USA and the Netherlands report that Th17 cells are able to remodel meninges-derived stroma, and thus, support the recruitment of inflammatory cells in the brain.

This is achieved by the collaborations of Th17–lymphotoxin (LT) αβ pathways, and through cytokines actions boosting resident Th17 cells activity.

Importantly, the study shows that TLTs in the brain meninges are linked to subpial demyelination and astrogliosis, and that IL-17, IL-22 and LT contribute to meningeal inflammation during the early stages of experimental autoimmune encephalitis (EAE).

The results of this study may have important implications for autoimmune diseases such as multiple sclerosis (MS). The authors argue that during the very early stages of MS, LT αβ+ Th17 cells circulating in the cerebrospinal fluid (CSF) might begin to remodel meningeal stroma. With the disease progression, and through some mechanisms described in this study, “soluble factors emanating from the meninges might cause a more indolent process of demyelination, astrocytosis, and axonal degeneration”.

Source: Immunity, 2015, 43:1160. doi: 10.1016/j.immuni.2015.11.010.
Read more: cell.com


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Source: Cover Image: Graphical Abstract from: Integration of Th17- and Lymphotoxin-Derived Signals Initiates Meningeal-Resident Stromal Cell Remodeling to Propagate Neuroinflammation; Immunity, 2015, 43:1160; Authors: Natalia Pikor, Jillian Astarita, Leslie Summers-Deluca, Samuel Ludwin, Shannon J. Turley, Jennifer L. Gommerman; Credit: cell.com; http://www.cell.com/immunity/abstract/S1074-7613%2815%2900462-8?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1074761315004628%3Fshowall%3Dtrue Public domain.

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