Coordination of Immune-Stroma Crosstalk by IL-6 Family Cytokines

Abstract

Stromal cells are a subject of rapidly growing immunological interest based on their ability to influence virtually all aspects of innate and adaptive immunity. Present in every bodily tissue, stromal cells complement the functions of classical immune cells by sensing pathogens and tissue damage, coordinating leukocyte recruitment and function, and promoting immune response resolution and tissue repair. These diverse roles come with a price: like classical immune cells, inappropriate stromal cell behavior can lead to various forms of pathology, including inflammatory disease, tissue fibrosis, and cancer. An important immunological function of stromal cells is to act as information relays, responding to leukocyte-derived signals and instructing leukocyte behavior in kind. In this regard, several members of the interleukin-6 (IL-6) cytokine family, including IL-6, IL-11, oncostatin M (OSM), and leukemia inhibitory factor (LIF), have gained recognition as factors that mediate crosstalk between stromal and immune cells, with diverse roles in numerous inflammatory and homeostatic processes. This review summarizes our current understanding of how IL-6 family cytokines control stromal-immune crosstalk in health and disease, and how these interactions can be leveraged for clinical benefit.

Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle

“…The GO term positive regulation of cell proliferation was also enriched for commonly up‐regulated genes. Based on the specific genes that annotated to this category, this may relate to proliferation of fibroblasts or other non‐muscle cell types based on the known role of galectin 3 and IL‐6/oncostatin M signalling pathways in activation of fibrosis and inflammation . PI3K‐Akt signalling was an enriched KEGG pathway for commonly up‐regulated genes; however, Ddit4 and Eif4ebp1 annotated to this category, which are inhibitors of the PI3K‐Akt pathway.…”

Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease

“…In particular, immature Mfs, as well as cDC2, induced intestinal inflammation through fibroblast activation via oncostatin M/OSMR signaling, which increased in IBD patients and predicted anti-TNF therapy response (275,301). However, even if OSM induced IL-11 expression by activated fibroblast (275), which is known to be a major fibrotic component (302), whether OSM promotes intestinal fibrosis in IBD patients remains to be determined.…”

Interleukin-11 is a Marker for Both Cancer- and Inflammation-Associated Fibroblasts that Contribute to Colorectal Cancer Progression

“…Interleukin (IL)-11 is a member of the IL-6 family, and exhibits pleiotropic functions, including hematopoiesis, bone development, tissue repair, and tumor development 11, 12 . The IL-11 receptor comprises IL-11Rα1, which binds IL-11, and gp130, which transmits signals to the nucleus via Janus kinase (JAK) activation 13 . JAKs phosphorylate STAT3, and phosphorylated STAT3 enters the nucleus where it activates the transcription of various target genes associated with cell proliferation and apoptosis suppression 14,15,16,17 .…”