PT  - JOURNAL ARTICLE
AU  - Dongkyun Kim
AU  - Sohee Kim
AU  - Zhinan Yin
AU  - Booki Min
TI  - Cell type specific IL-27p28 (IL-30) deletion uncovers an unexpected pro-inflammatory property of IL-30 in autoimmune inflammation
AID  - 10.1101/2022.01.03.474823
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.03.474823
4099  - http://biorxiv.org/content/early/2022/01/03/2022.01.03.474823.short
4100  - http://biorxiv.org/content/early/2022/01/03/2022.01.03.474823.full
AB  - IL-27 is an IL-12 family cytokine with potent immunoregulatory properties, capable of modulating inflammatory responses, including autoimmunity. While extensive studies have been performed to investigate the major target cells of IL-27 mediating its functions, the source of IL-27 especially during tissue specific autoimmune inflammation has not formally been tested. IL-27p28 subunit, also known as IL-30, was initially discovered as an IL-27-specific subunit, and its expression has thus been used as a surrogate for IL-27. However, there is emerging evidence that IL-27p28 can be secreted without Ebi3, a subunit that forms IL-27 with IL-27p28. Furthermore, IL-27p28 was also reported to act as a negative regulator antagonizing IL-27. In this study, we utilized various cell type specific IL-27p28-deficient mouse models and examined the major source of IL-27p28 in T cell mediated autoimmune neuroinflammation. We found that dendritic cell-derived IL-27p28 is dispensable for the disease development but that IL-27p28 expressed by infiltrating and CNS resident APC subsets, namely, infiltrating monocytes, microglia, and astrocytes, play an essential role in limiting inflammation. Unexpectedly, we observed that cell type specific IL-27p28 deficiency expressing severe disease phenotype is associated with dysregulated IL-27p28 expression in otherwise unaffected APC subsets, suggesting that disproportionate IL-27p28 expressed may increase disease susceptibility. Indeed, systemic recombinant IL-30 administration also induced severe disease. Taken together, our results uncover a pro-inflammatory property of IL-30 that supports encephalitogenic immunity in vivo.Competing Interest StatementThe authors have declared no competing interest.