Abstract Number: OC 28.3
Meeting: ISTH 2021 Congress
Background: Monocytes are immune cells which differentiate into subsets through sequential transition. The life-time differs between the individual subsets ranging from 1 day to 1 week. Interleukin-4 (IL-4) signaling has been shown promote the proliferation and polarization of macrophages independently of colony-stimulating factors.
Aims: It is unknown if IL-4 influences monocyte homeostasis. We studied the relevance of IL-4/13 on monocytes during homeostasis in mice lacking functional IL-4 receptors.
Methods: Leukocyte counts were analyzed in blood and tissues. Apoptosis of monocytes was assessed by RNA sequencing and histochemical staining in the spleen. Human monocytes were stimulated with IL-4 to study its effect on survival in vitro. The effect of IL-4 receptor alpha signaling on the lifespan of monocyte subsets was studied in knockout mice. Further, IL-4 was applied subcutaneously to wildtype mice to evaluate the impact of increased IL-4 levels on monocyte lifespan. The physiological relevance of our findings was finally studied in a sterile peritonitis model.
Results: We show that IL-4 acts as homeostatic factor regulating circulating monocyte amounts. We found that IL-4 receptor alpha knockout led to the halving of monocytes in blood without altering monocytopoiesis in bone marrow. Analysis of splenic monocytes by RNAseq and immunostaining revealed an increase in apoptotic spleen monocytes of IL-4Rα-/- mice. Further, we demonstrated that basal IL-4 receptor activity directly regulates the lifespan of monocytes in vivo. Knockout of IL-4Rα reduced the lifespan of Ly6Clow monocytes in circulation, whereas subcutaneous applied IL-4 further prolonged it. Finally, IL-4Rα knockout reduced the recruitment of monocytes upon inflammatory stimulation.
Conclusions: We identified a novel role of basal IL-4 levels in regulating the lifespan of monocytes in vivo.
To cite this abstract in AMA style:Haider P, Kral-Pointner J, Salzmann M, Bleichert S, Schrottmaier W, Kaun C, Brekalo M, Hengstenberg C, Fischer M, Speidl W, Huber K, Knapp S, Brombacher F, Brostjan C, Wojta J, Hohensinner P. Interleukin-4 Signaling Enhances Survival of Circulating Monocytes in vivo [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/interleukin-4-signaling-enhances-survival-of-circulating-monocytes-in-vivo/. Accessed May 20, 2022.
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