Granulocyte–macrophage colony‐stimulating factor–stimulated human macrophages demonstrate enhanced functions contributing to T‐cell activation. Issue 1 (5th November 2022)

• Record Type: Journal Article
• Authors: Farzam‐kia, Negar; Lemaître, Florent; Carmena Moratalla, Ana; Carpentier Solorio, Yves; Da Cal, Sandra; Jamann, Hélène; Klement, Wendy; Antel, Jack; Duquette, Pierre; Girard, Jean Marc; Prat, Alexandre; Larochelle, Catherine; Arbour, Nathalie
• Is Part Of: Immunology and cell biology. Volume 101:Issue 1(2023)
• Page Start: 65
• Page End: 77
• Publication Date: 2022-11-05
• Subjects: CD8+ T lymphocytes -- chemokine -- cytokine -- GM‐CSF -- macrophage -- microglia; Immunology -- Periodicals; Cytology -- Periodicals; 616.079
• DOI: 10.1111/imcb.12600
• Languages: English
• ISSNs: 0818-9641

Abstract

Abstract: Granulocyte–macrophage colony‐stimulating factor (GM‐CSF) has been implicated in numerous chronic inflammatory diseases, including multiple sclerosis (MS). GM‐CSF impacts multiple properties and functions of myeloid cells via species‐specific mechanisms. Therefore, we assessed the effect of GM‐CSF on different human myeloid cell populations found in MS lesions: monocyte‐derived macrophages (MDMs) and microglia. We previously reported a greater number of interleukin (IL)‐15 + myeloid cells in the brain of patients with MS than in controls. Therefore, we investigated whether GM‐CSF exerts its deleterious effects in MS by increasing IL‐15 expression on myeloid cells. We found that GM‐CSF increased the proportion of IL‐15 + cells and/or IL‐15 levels on nonpolarized, M1‐polarized and M2‐polarized MDMs from healthy donors and patients with MS. GM‐CSF also increased IL‐15 levels on human adult microglia. When cocultured with GM‐CSF–stimulated MDMs, activated autologous CD8 + T lymphocytes secreted and expressed significantly higher levels of effector molecules (e.g. interferon‐γ and GM‐CSF) compared with cocultures with unstimulated MDMs. However, neutralizing IL‐15 did not attenuate enhanced effector molecule expression on CD8 + T lymphocytes triggered by GM‐CSF–stimulated MDMs. We showed that GM‐CSF stimulation of MDMs increased their expression of CD80 and ICAM‐1 and their secretion of IL‐6, IL‐27 and tumor necrosis factor. These molecules could participate in boosting the effector properties of CD8 + T lymphocytes independently of IL‐15. By contrast, GM‐CSF did not alter CD80, IL‐27, tumor necrosis factor and chemokine (C–X–C motif) ligand 10 expression/secretion by human microglia. Therefore, our results underline the distinct impact of GM‐CSF on human myeloid cells abundantly present in MS lesions. Abstract : We investigated the effect of granulocyte–macrophage colony‐stimulating factor (GM‐CSF) on human myeloid cells found in multiple sclerosis (MS) lesions: macrophages and microglia. GM‐CSF increased the expression of costimulatory molecules, cytokines and chemokines by macrophages. Coculture assays of autologous, human macrophages and CD8 + T lymphocytes showed that GM‐CSF–stimulated macrophages triggered a greater response in CD8 + T lymphocytes. GM‐CSF had a more modest effect on human adult microglia, highlighting the distinct impact of GM‐CSF on myeloid cells abundantly present in MS lesions.