Tissue regulatory T cells and neural repair

Abstract

Inflammation and immune responses after tissue injury play pivotal roles in the pathology, resolution of inflammation, tissue recovery, fibrosis and remodeling. Regulatory T cells (Tregs) are the cells responsible for suppressing immune responses and can be activated in secondary lymphatic tissues, where they subsequently regulate effector T cell and dendritic cell activation. Recently, Tregs that reside in non-lymphoid tissues, called tissue Tregs, have been shown to exhibit tissue-specific functions that contribute to the maintenance of tissue homeostasis and repair. Unlike other tissue Tregs, the role of Tregs in the brain has not been well elucidated because the number of brain Tregs is very small under normal conditions. However, we found that Tregs accumulate in the brain at the chronic phase of ischemic brain injury and control astrogliosis through secretion of a cytokine, amphiregulin (Areg). Brain Tregs resemble other tissue Tregs in many ways but, unlike the other tissue Tregs, brain Tregs express neural-cell-specific genes such as the serotonin receptor (Htr7) and respond to serotonin. Administering serotonin or selective serotonin reuptake inhibitors (SSRIs) in an experimental mouse model of stroke increases the number of brain Tregs and ameliorates neurological symptoms. Knowledge of brain Tregs will contribute to the understanding of various types of neuroinflammation.

Transcriptional Regulation of Differentiation and Functions of Effector T Regulatory Cells

“…The majority of eTreg cells migrate to and accumulate in non-lymphoid peripheral tissues and inflamed sites, probably due to a decrease in CD62L and CCR7 expression and a concomitant increase in the expression of various chemokine receptors (e.g., CCR4, CCR6, and CCR10) and adhesion molecules (e.g., KLRG1, CD103) [16,17,22,23]. eTreg cells can reside in non-lymphoid peripheral tissues, as tissue Treg cells, and play a role not only in the maintenance of immune homeostasis but also in tissue repair and regeneration [25,26,27,28,29,30,31]. For example, visceral adipose tissue (VAT)-Treg cells accumulate in and suppress the inflammation of adipose tissue, thereby regulating insulin resistance [32,33,34].…”

Subconjunctival Injection of Regulatory T Cells Potentiates Corneal Healing Via Orchestrating Inflammation and Tissue Repair After Acute Alkali Burn

“…47 After administrating rmAreg, corneal recovery was enhanced with an increase in corneal restoration and cells staining positive for Ki67, while the efficacy of Treg treatment was partly suppressed after using anti-Areg, suggesting that Areg might be necessary for the beneficial function of Tregs in acute corneal restoration. Combined with other reports on the association between Tregs and Areg, 46,48 it was speculated that Tregs exerted a protective role in corneal epithelial proliferation via Areg. Additionally, the supplementation of Areg downregulated the inflammation with decreased expression levels of inflammatory cytokines in corneas, while anti-Areg upregulated the inflammation; this was consistent with the reports on Areg modulating immune responses.…”

Immune Privilege: The Microbiome and Uveitis

“…to neuro-BD and Bacteroides with multiple sclerosis (170). Importantly, Treg which are considered to play a role in maintaining IP in the retina (43,44,171,172) and brain (173)(174)(175) have demonstrated clear tissue adaptation at the barrier sites of the skin and the intestine (176) and it is likely that they do so at sites of the BRB and BBB. Thus, in terms of uveitis there is no clear pattern of disease susceptibility.…”