Role of CD4+ T-cells for regulating splenic myelopoiesis and monocyte differentiation after experimental myocardial infarction

• Published in: Basic research in cardiology Vol. 119; no. 2; pp. 261 - 275
• Main Authors: Gladow, Nadine, Hollmann, Claudia, Weirather, Johannes, Ding, Xin, Burkard, Matthias, Uehlein, Sabrina, Bharti, Richa, Förstner, Konrad, Kerkau, Thomas, Beyersdorf, Niklas, Frantz, Stefan, Ramos, Gustavo, Hofmann, Ulrich
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-04-2024; Springer Nature B.V
• Subjects: Cardiology; CD25 antigen; CD4 antigen; Cell differentiation; Cells (biology); Depletion; Differentiation; Foxp3 protein; Gene expression; Healing; Heart attacks; Inflammation; Lymphocytes T; Macrophages; Medicine; Medicine & Public Health; Monocytes; Myelopoiesis; Myocardial infarction; Myocardium; Original Contribution; Paracrine signalling; Progenitor cells; Spleen; γ-Interferon; Myocardial infarction; Monocytes; Lymphocytes; Treg
• ISSN: 1435-1803; 0300-8428; 1435-1803
• DOI: 10.1007/s00395-024-01035-3

Myocardial infarction (MI) induces the generation of proinflammatory Ly6C
high
monocytes in the spleen and the recruitment of these cells to the myocardium. CD4
+
Foxp3
+
CD25
+
T-cells (Tregs) promote the healing process after myocardial infarction by engendering a pro-healing differentiation state in myocardial monocyte-derived macrophages. We aimed to study the effects of CD4
+
T-cells on splenic myelopoiesis and monocyte differentiation. We instigated MI in mice and found that MI-induced splenic myelopoiesis is abrogated in CD4
+
T-cell deficient animals. Conventional CD4
+
T-cells promoted myelopoiesis in vitro by cell–cell-contact and paracrine mechanisms, including interferon-gamma (IFN-γ) signalling. Depletion of regulatory T-cells enhanced myelopoiesis in vivo, as evidenced by increases in progenitor cell numbers and proliferative activity in the spleen 5 days after MI. The frequency of CD4
+
T-cells-producing factors that promote myelopoiesis increased within the spleen of Treg-depleted mice. Moreover, depletion of Tregs caused a proinflammatory bias in splenic Ly6C
high
monocytes, which showed predominantly upregulated expression of IFN-γ responsive genes after MI. Our results indicate that conventional CD4
+
T-cells promote and Tregs attenuate splenic myelopoiesis and proinflammatory differentiation of monocytes.