Table 1.
Involvement of GM-CSF and IL-3 in disease pathogenesis.
| Disease | Cytokine Involved | Description | References |
|---|---|---|---|
| Pulmonary alveolar proteinosis | GM-CSF | Decreased bioavailability of GM-CSF leads to impaired maturation of alveolar macrophages and accumulation of surfactant and related products within lung alveoli. | [4,6,7,8] |
| Myocardial infarction | GM-CSF | GM-CSF produced by cardiac fibroblasts promotes inflammation and leukocyte accrual and impairs wound healing upon myocardial infarction. | [102] |
| Kawasaki disease | GM-CSF | GM-CSF produced by cardiac fibroblasts stimulates cytokine and chemokine production by resident macrophages, thereby promoting cardiac inflammation. | [104] |
| Myocarditis | GM-CSF | IL-23-induced, CD4+ T cell-derived GM-CSF drives cardiac inflammation in an experimental model of myocarditis. | [97] |
| Acute rheumatic fever | GM-CSF | PBMCs isolated from acute rheumatic fever patients and stimulated in vitro with GAS produce more CD4+ T cell-derived GM-CSF compared to healthy controls. | [105] |
| Inflammatory bowel disease | GM-CSF | The role of GM-CSF in IBD is context dependent. IL-23-induced GM-CSF drives the pathogenesis of T cell-driven and ILC-driven experimental models of colitis. DSS-induced epithelial damage is exacerbated in GM-CSF deficient mice. Adoptive transfer of GM-CSF-treated murine monocytes ameliorates T cell-dependent experimental colitis. | [17,18,34,47,48,106,107] |
| Lupus nephritis | IL-3 | Administration of exogenous IL-3 and an anti-IL-3-blocking antibody to MRL/lpr mice (which develop a spontaneous autoimmune disease that resembles human systemic lupus erythematosus), respectively, promotes and restrains lupus nephritis progression. | [90] |
| Hematologic malignancies | IL-3 | IL-3 is a survival factor for several malignant hematopoietic cell lineages, especially acute myeloid leukemia where CD123 expression on cancer cells correlates with reduced patient survival. | [49,50,51] |
| Allergic asthma | GM-CSF and IL-3 | Epithelial cell-derived GM-CSF promotes DC activation and Th2 immunity in an experimental model of dust mite-elicited allergic airway inflammation. Basophil-derived IL-3 induces the development of AHR in a model of allergic airway inflammation induced by systemic injections of OVA/alum followed by intranasal OVA challenge. | [19,23,24,25] |
| Multiple sclerosis | GM-CSF and IL-3 | GM-CSF promotes the development of EAE by inducing the expression of a pathogenic program in monocytes. GM-CSF can be produced by both CD4+ T cells and memory B cells. Encephalitogenic CD4+ T cells also express IL-3. However, conflicting results exist on the role of this cytokine in the development and progression of EAE. | [16,26,27,28,29,30,31,71,72,73,74,75] |
| Aortic dissection | GM-CSF and IL-3 | IL-3 elicits macrophage production of MMP12 and is required for the development of chemically induced thoracic aortic aneurysm and dissection. GM-CSF synergizes with aortic inflammation elicited by CaCl2 and Ang II to induce aortic dissection/intramural hematoma. | [95,96] |
| Atherosclerosis | GM-CSF and IL-3 | Both GM-CSF and IL-3 aggravate atherosclerosis development by promoting formation of atherosclerotic plaques, extramedullary hematopoiesis and monocyte differentiation, DC generation and Th1 polarization. | [42,98,99,100,101] |
| Sepsis | GM-CSF and IL-3 | In experimental models of CLP-induced sepsis, GM-CSF produced by IRA B cells enhances bacterial clearance and exerts a protective role. Conversely, IL-3 promotes myelopoiesis and cytokine storm therefore playing a detrimental role. | [11,40] |
| Rheumatoid arthritis | GM-CSF and IL-3 | GM-CSF derived from ILCs, stromal and T cells plays a prominent role in the development and progression of murine models of arthritis. IL-3 has been reported to either attenuate or exacerbate arthritis symptoms. | [76,77,78,79,80,82,83] |
Abbreviations: AHR, airway hyperresponsiveness; Ang II, angiotensin II; CLP, cecal ligation and puncture; DC, dendritic cell; DSS, dextran sulfate sodium; EAE, experimental autoimmune encephalomyelitis; GAS, group A streptococcus; IBD, inflammatory bowel disease; ILCs, innate lymphoid cells; IRA B cells, innate response activator B cells; MMP12, matrix metalloprotease 12; OVA, ovalbumin; PBMCs, peripheral blood mononuclear cells.