| First Author | Zarin P | Year | 2023 |
| Journal | Proc Natl Acad Sci U S A | Volume | 120 |
| Issue | 14 | Pages | e2221255120 |
| PubMed ID | 36972453 | Mgi Jnum | J:341200 |
| Mgi Id | MGI:7532510 | Doi | 10.1073/pnas.2221255120 |
| Citation | Zarin P, et al. (2023) Treg cells require Izumo1R to regulate gammadeltaT cell-driven inflammation in the skin. Proc Natl Acad Sci U S A 120(14):e2221255120 |
| abstractText | Izumo1R is a pseudo-folate receptor with an essential role in mediating tight oocyte/spermatozoa contacts during fertilization. Intriguingly, it is also expressed in CD4(+) T lymphocytes, in particular Treg cells under the control of Foxp3. To understand Izumo1R function in Treg cells, we analyzed mice with Treg-specific Izumo1r deficiency (Iz1rTrKO). Treg differentiation and homeostasis were largely normal, with no overt autoimmunity and only marginal increases in PD1(+) and CD44(hi) Treg phenotypes. pTreg differentiation was also unaffected. Iz1rTrKO mice proved uniquely susceptible to imiquimod-induced, gammadeltaT cell-dependent, skin disease, contrasting with normal responses to several inflammatory or tumor challenges, including other models of skin inflammation. Analysis of Iz1rTrKO skin revealed a subclinical inflammation that presaged IMQ-induced changes, with an imbalance of Rorgamma+ gammadeltaT cells. Immunostaining of normal mouse skin revealed the expression of Izumo1, the ligand for Izumo1R, electively in dermal gammadeltaT cells. We propose that Izumo1R on Tregs enables tight contacts with gammadeltaT cells, thereby controlling a particular path of skin inflammation. |
