Thy1⁺Sca1⁺ innate lymphoid cells infiltrate the CNS during autoimmune inflammation, but do not contribute to disease development

Abstract

IL-23 is absolutely crucial for the development of T-cell driven autoimmune disease in mice. Even though IL-23 is widely held to be involved in the stabilization of IL-17-secreting T cells, naïve T cells lack the IL-23 receptor. Thus, the primary cellular target of IL-23 in the context of autoimmunity is a subject of some debate. Innate lymphoid cells (ILCs) are a recently discovered family of lymphocytes being involved in early host defense, particularly at mucosal epithelial surfaces. Given the fact that RORγt-dependent ILCs (group 3 ILCs) constitutively express the IL-23-receptor, and that they have been implicated in intestinal autoimmunity, we hypothesized that ILCs could contribute to the early development of autoimmune neuroinflammation. Through systematic analysis, we detected a sizable population of Thy1 + Sca1 + ILCs in the inflamed CNS tissue. CNS-infiltrating ILCs were characterized by expression of the IL-7-receptor and production of proinflammatory IL-17 and IFN-γ. Furthermore, genetic fate-mapping revealed their dependence on the transcription factor RORγt. However, upon specific in vivo ablation of this cell population, we found that they do not influence the course of the disease.

Group 3 innate lymphoid cells accumulate and exhibit disease-induced activation in the meninges in EAE

“…In contrast to our current studies and those of Columba-Cabezas et al [66], which indirectly support a role for ILC3s in EAE, a recent publication by Mair and Becher provides evidence that ILCs do not contribute to EAE [78]. The authors identified a population of Thy1.1+ Sca-1+ ILCs in the CNS in disease.…”

Innate Lymphoid Cells in Inflammation and Immunity

“…An increased frequency of ILC3s was shown to associate with MS and treatment with the anti-CD25-blocking antibody, daclizumab, resulted in the reduction of ILC3s in peripheral blood and a decrease in intrathecal inflammation. However, the effects of anti-CD25 treatment extend beyond ILC3s, and an initial report using a mouse model of experimental autoimmune encephalomyelitis (EAE) failed to show a causative role for ILC3s in this disease (Mair and Becher, 2014). ILC3s Crosstalk with Adaptive T and B Cells New functions for ILC3s in influencing adaptive immunity have recently been discovered.…”

Mast Cells and Innate Lymphoid Cells: Underappreciated Players in CNS Autoimmune Demyelinating Disease

“…An incontrovertible role for ILCs in EAE has been difficult to prove because, as for mast cells, there is no selective ILC2-knockout mouse. Mair and Becher were among the first to examine a possible ILC contribution to EAE using a cell depletion approach ( 104 ). ILCs, defined as Thy1 + Sca1 + cells, are increased in the CNS of C57BL/6 mice with EAE.…”