| First Author | Michiels C | Year | 2021 |
| Journal | J Invest Dermatol | Volume | 141 |
| Issue | 11 | Pages | 2668-2678.e6 |
| PubMed ID | 33992648 | Mgi Jnum | J:318651 |
| Mgi Id | MGI:6789614 | Doi | 10.1016/j.jid.2021.04.016 |
| Citation | Michiels C, et al. (2021) A Targetable, Noncanonical Signal Transducer and Activator of Transcription 3 Activation Induced by the Y-Less Region of IL-22 Receptor Orchestrates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice. J Invest Dermatol 141(11):2668-2678.e6 |
| abstractText | Exacerbated IL-22 activity induces tissue inflammation and immune disorders such as psoriasis. However, because IL-22 is also essential for tissue repair and defense at barrier interfaces, targeting IL-22 activity to treat psoriasis bears the risk of deleterious effects at mucosal sites such as the gut. We previously showed in vitro that IL-22 signaling relies on IL-22 receptor alpha (IL-22Ralpha) Y-dependent and -independent pathways. The second depends on the C-terminal Y-less region of IL-22Ralpha and leads to a massive signal transducer and activator of transcription 3 (STAT3) activation. Because STAT3 activation is associated with the development of psoriasis, we hypothesized that the specific inhibition of the noncanonical STAT3 activation by the Y-less region of IL-22Ralpha could reduce psoriasis-like disease while leaving intact its tissue defense functions in the gut. We show that mice expressing a C-terminally truncated version of IL-22Ralpha (DeltaCter(mut/mut) mice) are protected from the development of psoriasis-like dermatitis lesions induced by imiquimod to a lesser extent than Il22ra(-/-) mice. In contrast, only Il22ra(-/-) mice lose weight after Citrobacter rodentium infection. Altogether, our data suggest that specific targeting of the noncanonical STAT3 activation by IL-22 could serve to treat psoriasis-like skin inflammation without affecting IL-22dependent tissue repair or barrier defense at other sites. |
