| First Author | A Verghese D | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 6 | Pages | 2186-2198 |
| PubMed ID | 29436411 | Mgi Jnum | J:258846 |
| Mgi Id | MGI:6121655 | Doi | 10.4049/jimmunol.1701638 |
| Citation | A Verghese D, et al. (2018) T Cell Expression of C5a Receptor 2 Augments Murine Regulatory T Cell (TREG) Generation and TREG-Dependent Cardiac Allograft Survival. J Immunol 200(6):2186-2198 |
| abstractText | C5aR2 (C5L2/gp77) is a seven-transmembrane spanning receptor that binds to C5a but lacks motifs essential for G protein coupling and associated signal transduction. C5aR2 is expressed on immune cells, modulates various inflammatory diseases in mice, and has been shown to facilitate murine and human regulatory T cell (TREG) generation in vitro. Whether and how C5aR2 impacts in vivo TREG generation and pathogenic T cell-dependent disease models have not been established. In this article, we show that murine T cells express and upregulate C5aR2 during induced TREG (iTREG) generation and that the absence of T cell-expressed C5aR2 limits in vivo iTREG generation following adoptive transfer of naive CD4(+) T cells into Rag1(-/-) recipients. Using newly generated C5aR2-transgenic mice, we show that overexpression of C5aR2 in naive CD4(+) T cells augments in vivo iTREG generation. In a model of TREG-dependent cardiac allograft survival, recipient C5aR2 deficiency accelerates graft rejection associated with lower TREG/effector T cell ratios, whereas overexpression of C5aR2 in immune cells prolongs graft survival associated with an increase in TREG/effector T cell ratios. T cell-expressed C5aR2 modulates TREG induction without altering effector T cell proliferation or cytokine production. Distinct from reported findings in neutrophils and macrophages, TREG-expressed C5aR2 does not interact with beta-arrestin or inhibit ERK1/2 signaling. Rather, cumulative evidence supports the conclusion that C5aR2 limits C5aR1-initiated signals known to inhibit TREG induction. Together, the data expand the role of C5aR2 in adaptive immunity by providing in vivo evidence that T cell-expressed C5aR2 physiologically modulates iTREG generation and iTREG-dependent allograft survival. |
