Irgm1 is required for the inflammatory function of M1 macrophage in early experimental autoimmune encephalomyelitis
Bibliographic record
Abstract
Abstract The classically activated (M1) macrophage has been shown to play an indispensable role in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). However, most studies focus on the effect of macrophage on CNS demyelination of EAE; whether the M1 macrophage participates in early EAE and the molecular mechanism underlying remains unclear. Here, we showed that the immunity-related GTPase family member 1 (Irgm1), also known as LRG-47, was expressed in M1 macrophages of draining lymph nodes (dLNs) from C57BL/6 mice with early EAE, and the IRGM1 heterozygote substantially reduced M1 macrophage accumulation in dLNs and spleen of the primary EAE stage. In vitro silence of IRGM1 in M1 macrophages impaired NOS2 expression and inflammatory cytokine release. We also found that IRGM1 knockout (Irgm1−/−) in M1 macrophages increased Akt activation but attenuated NF-κB p65 activation, which may reveal Irgm1-mediated mechanisms of action. Interestingly, macrophage depletion in vivo inhibited Th1/Th17 differentiation in the spleen and promoted regulatory T cell (Treg) polarization in dLNs at 7 d postimmunization (dpi). Moreover, we observed that M1 macrophages in vitro promoted Th1/Th17 differentiation, which was reversed by treatment with IRGM1 small interfering RNA (siRNA), anti-TNF-α, or anti-IL-1β mAb. These results suggest that the M1 macrophage may promote Th1/Th17 cell differentiation during the early EAE, and the proinflammatory function of M1 cells requires Irgm1.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".