| First Author | Wermeling F | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 33 | Pages | 13487-91 |
| PubMed ID | 23898202 | Mgi Jnum | J:200690 |
| Mgi Id | MGI:5509091 | Doi | 10.1073/pnas.1312525110 |
| Citation | Wermeling F, et al. (2013) Acute inflammation primes myeloid effector cells for anti-inflammatory STAT6 signaling. Proc Natl Acad Sci U S A 110(33):13487-91 |
| abstractText | The anti-inflammatory drug high-dose intravenous immunoglobulin, widely used to suppress inflammation, depends on a specific alpha-2,6-sialylated glycoform of IgG Fc to induce Interleukin 4 (IL-4) and Signal Transducer and Activator of Transcription 6 (STAT6) signaling for its activity. Here we show that anti-inflammatory activities of IL-4 can be attributed to the direct action of this cytokine on myeloid effector cells, depending on their expression of the IL-4 receptor alpha chain (IL-4Ralpha/CD124). However, in their basal state, these cells express low levels of IL-4Ralpha and would not be expected to result in significant signaling compared with other cell populations. This apparent paradox can be explained by the observation that during inflammation, triggered by a variety of stimuli (including autoantibodies, adjuvants, and TLR ligands), IL-4Ralpha is up-regulated specifically on these cells, priming them for STAT6 signaling. The regulation is mediated by a soluble, proteinase K-sensitive factor, released to the circulation by bone marrow-derived, non-B/non-T cells found in several organs, including the lungs, and fat. We propose that this regulation is part of a homeostatic mechanism to limit excessive inflammation and tissue damage. High-dose intravenous immunoglobulin thus exploits an endogenous feedback loop, general to inflammation, that could be further targeted for therapeutic purposes. |
