Ocular immune privilege in action: the living eye imposes unique regulatory and anergic gene signatures on uveitogenic T cells 9087
Year: 2025
Type: article
Abstract: Description The healthy eye limits destructive inflammation, a phenomenon known as immune privilege, but despite that, it is subject to autoimmune uveitis driven by retina-specific effector T cells. Our previous results showed that naïve retina-specific T cells were all primed within one week after being injected into healthy mice eyes. About 1/3 converted to functional Foxp3+ Tregs; the rest did not become Tregs but failed to elicit pathology. However, investigation of their fate and function was hindered by the limited number of cells retrievable from mouse eyes. In the current study, we analyzed the transcriptomic changes in the eye-primed retina-specific T cells at the single-cell level. Our data revealed unique transcriptional signatures not only in the Foxp3+ Tregs, but also in the non-converted populations. Notably, most non-Foxp3 T cells appeared to be phenotypically anergic (Ctla4, Lag3, Cblb, and Dgkz), with high expression of immunosuppressive genes (e.g. Tgfb1). Functionally, those Foxp3 negative T cells were hyporesponsive to restimulation with splenic APC and antigen; and did not exhibit significant regulatory activity. Trajectory analyses suggested that the Tregs and anergic T cells differentiated in parallel, rather than sequentially, from a common proliferative precursor. Our findings offer novel molecular insights into the complex phenomenon of ocular immune privilege and could instruct approaches to modulate ocular inflammatory disease. Funding Sources Supported by NIH/NEI EY000184. Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)
Source: The Journal of Immunology
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416451529
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