Faculty, Staff and Student Publications
Language
English
Publication Date
1-23-2025
Journal
Immunohorizons
DOI
10.1093/immhor/vlae004
PMID
39846845
PMCID
PMC11841978
PubMedCentral® Posted Date
1-23-2025
PubMedCentral® Full Text Version
Post-print
Abstract
CD73 is ubiquitously expressed and regulates critical functions across multiple organ systems. The sequential actions of CD39 and CD73 accomplish the conversion of adenosine triphosphate to adenosine and shift the adenosine triphosphate-driven proinflammatory immune cell milieu toward an anti-inflammatory state. This immunological switch is a major mechanism by which regulatory T (Treg) cells control inflammation. Foxp3 engages in Treg development and function. Foxp3 mutations result in the scurfy (SF) mouse phenotype and a rapidly lethal lymphoproliferative syndrome. We generated double knockout (KO) mouse (CD73KOSF) by breeding heterozygous Foxp3sf/J females to CD73KO male mice to remove host CD73. We initially aimed to use these mice to identify a specific probiotic-CD73 effect, previously shown for Limosilactobacillus reuteri DSM 17938. We expected CD73 deletion to enhance the severity of autoimmunity in SF mice. However, we unexpectedly observed that KO of host CD73 in SF mice clinically reduced the severity of autoimmunity including reduced ear thickness, increased ear size, and less deformed ears, along with less dry and brittle skin. KO of CD73 in SF mice significantly reduced the numbers of CD4+ and CD8+T cells in spleen and blood. We identified that KO of CD73 in SF mice reduced the numbers of T cells in the thymus compared with those in SF mice, indicating that the milder clinical phenotype may be due to reduced central and peripheral lymphoproliferation. These new findings suggest targeting CD73 could improve T cell-mediated dermatitis, one of the most common symptoms in Treg deficiency-associated primary immune deficiencies.
Keywords
Animals, 5'-Nucleotidase, Mice, Autoimmunity, Mice, Knockout, Female, T-Lymphocytes, Regulatory, Male, Forkhead Transcription Factors, Limosilactobacillus reuteri, dermatitis, IPEX syndrome, primary immune deficiency, regulatory T cell, scurfy, thymocytes
Published Open-Access
yes
Recommended Citation
Okeugo, Beanna; Armbrister, Shabba A; Daniel, Rhea C; et al., "Reduced Autoimmunity Associated With Deletion of Host CD73" (2025). Faculty, Staff and Student Publications. 4208.
https://digitalcommons.library.tmc.edu/uthmed_docs/4208