IL‐4 Promotes stromal cell expansion and Is critical for development Of A Type‐2, but not a type 1 immune response

IL‐4 is critical for differentiation of Th2 cells and antibody isotype switching, but our work demonstrated that it is produced in the peripheral lymph node (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‐4Rα 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 down‐regulation of Lymphotoxin alpha (LTα) and Lymphotoxin beta (LTβ), 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, lymph node re‐organization, or germinal center formation, while this process is IL‐4 independent following Type 1 immunization. Additionally, we found that Type 1 antigen mediated lymph node re‐organization is dependent on IFN‐γ 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.

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