| First Author | Cortes-Selva D | Year | 2019 |
| Journal | Eur J Immunol | Volume | 49 |
| Issue | 3 | Pages | 428-442 |
| PubMed ID | 30575951 | Mgi Jnum | J:274396 |
| Mgi Id | MGI:6283290 | Doi | 10.1002/eji.201847789 |
| Citation | Cortes-Selva D, et al. (2019) IL-4 promotes stromal cell expansion and is critical for development of a type-2, but not a type 1 immune response. Eur J Immunol 49(3):428-442 |
| abstractText | IL-4 is critical for differentiation of Th2 cells and antibody isotype switching, but our work demonstrated that it is produced in the peripheral LN under both Type 2, and Type 1 conditions, raising the possibility of other functions. We found that IL-4 is vital for proper positioning of hematopoietic and stromal cells in steady state, and the lack of IL-4 or IL-4Ralpha correlates with disarrangement of both follicular dendritic cells and CD31(+) endothelial cells. We observed a marked disorganization of B cells in these mice, suggesting that the lymphocyte-stromal cell axis is maintained by the IL-4 signaling pathway. This study showed that absence of IL-4 correlates with significant downregulation of Lymphotoxin alpha (LTalpha) and Lymphotoxin beta (LTbeta), critical lymphokines for the development and maintenance of lymphoid organs. Moreover, immunization of IL-4 deficient mice with Type 2 antigens failed to induce lymphotoxin production, LN reorganization, or germinal center formation, while this process is IL-4 independent following Type 1 immunization. Additionally, we found that Type 1 antigen mediated LN reorganization is dependent on IFN-gamma in the absence of IL-4. Our findings reveal a role of IL-4 in the maintenance of peripheral lymphoid organ microenvironments during homeostasis and antigenic challenge. |
