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

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2019 Jun 4

PMID 31156640

Citations 52

Authors

Nathaniel R West

Affiliations

Soon will be listed here.

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.

Citing Articles

Lymphoma-on-chip model reveals that lymph node stromal cells promote diffuse large B-cell lymphoma survival and migration.

Jouybar M, Mikula A, Zuidmeer N, Konijn T, de Jonge A, Roest H Mater Today Bio. 2025; 31:101544.

PMID: 40061210 PMC: 11889632. DOI: 10.1016/j.mtbio.2025.101544.

Astrocyte-Derived Interleukin 11 Modulates Astrocyte-Microglia Crosstalk via Nuclear Factor-κB Signaling Pathway in Sepsis-Associated Encephalopathy.

Zhu D, Wang P, Chen X, Wang K, Wu Y, Zhang M Research (Wash D C). 2025; 8:0598.

PMID: 39886603 PMC: 11780073. DOI: 10.34133/research.0598.

Unveiling the contribution of tumor-associated macrophages in driving epithelial-mesenchymal transition: a review of mechanisms and therapeutic Strategies.

Zhang Y, Ding X, Zhang X, Li Y, Xu R, Li H Front Pharmacol. 2024; 15:1404687.

PMID: 39286635 PMC: 11402718. DOI: 10.3389/fphar.2024.1404687.

The associations of oxidative stress and inflammatory markers with obesity in Iranian population: MASHAD cohort study.

Ghazizadeh H, Mansoori A, Sahranavard T, Nasrabadi M, Hadiloo K, Andalibi N BMC Endocr Disord. 2024; 24(1):56.

PMID: 38685027 PMC: 11057096. DOI: 10.1186/s12902-024-01590-9.

Therapeutic strategies to modulate gut microbial health: Approaches for sarcopenia management.

Das S, Preethi B, Kushwaha S, Shrivastava R Histol Histopathol. 2024; 39(11):1395-1425.

PMID: 38497338 DOI: 10.14670/HH-18-730.

References

Eickelberg O, Pansky A, Mussmann R, Bihl M, Tamm M, Hildebrand P . Transforming growth factor-beta1 induces interleukin-6 expression via activating protein-1 consisting of JunD homodimers in primary human lung fibroblasts. J Biol Chem. 1999; 274(18):12933-8. DOI: 10.1074/jbc.274.18.12933. View

BOZZA M, Bliss J, Maylor R, Erickson J, Donnelly L, Bouchard P . Interleukin-11 reduces T-cell-dependent experimental liver injury in mice. Hepatology. 1999; 30(6):1441-7. DOI: 10.1002/hep.510300616. View

Boileau C, Houde M, Dulude G, Clegg C, Perreault C . Regulation of extrathymic T cell development and turnover by oncostatin M. J Immunol. 2000; 164(11):5713-20. DOI: 10.4049/jimmunol.164.11.5713. View

Ihn H, Tamaki K . Oncostatin M stimulates the growth of dermal fibroblasts via a mitogen-activated protein kinase-dependent pathway. J Immunol. 2000; 165(4):2149-55. DOI: 10.4049/jimmunol.165.4.2149. View

Barton V, Hall M, Hudson K, Heath J . Interleukin-11 signals through the formation of a hexameric receptor complex. J Biol Chem. 2000; 275(46):36197-203. DOI: 10.1074/jbc.M004648200. View

Shimizu T, Shiratori K, Sawada T, Kobayashi M, Hayashi N, Saotome H . Recombinant human interleukin-11 decreases severity of acute necrotizing pancreatitis in mice. Pancreas. 2000; 21(2):134-40. DOI: 10.1097/00006676-200008000-00005. View

Hermanns H, Radtke S, Schaper F, Heinrich P, Behrmann I . Non-redundant signal transduction of interleukin-6-type cytokines. The adapter protein Shc is specifically recruited to rhe oncostatin M receptor. J Biol Chem. 2000; 275(52):40742-8. DOI: 10.1074/jbc.M005408200. View

Langdon C, Kerr C, Hassen M, Hara T, Arsenault A, Richards C . Murine oncostatin M stimulates mouse synovial fibroblasts in vitro and induces inflammation and destruction in mouse joints in vivo. Am J Pathol. 2000; 157(4):1187-96. PMC: 1850181. DOI: 10.1016/S0002-9440(10)64634-2. View

Schwaller J, Parganas E, Wang D, Cain D, Aster J, Williams I . Stat5 is essential for the myelo- and lymphoproliferative disease induced by TEL/JAK2. Mol Cell. 2000; 6(3):693-704. DOI: 10.1016/s1097-2765(00)00067-8. View

10.

Chen Q, Ghilardi N, Wang H, Baker T, Xie M, Gurney A . Development of Th1-type immune responses requires the type I cytokine receptor TCCR. Nature. 2000; 407(6806):916-20. DOI: 10.1038/35038103. View

11.

Chomarat P, Banchereau J, Davoust J, Palucka A . IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. Nat Immunol. 2001; 1(6):510-4. DOI: 10.1038/82763. View

12.

Georganas C, Liu H, Perlman H, Hoffmann A, Thimmapaya B, Pope R . Regulation of IL-6 and IL-8 expression in rheumatoid arthritis synovial fibroblasts: the dominant role for NF-kappa B but not C/EBP beta or c-Jun. J Immunol. 2000; 165(12):7199-206. DOI: 10.4049/jimmunol.165.12.7199. View

13.

Jones S, Horiuchi S, Topley N, Yamamoto N, Fuller G . The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J. 2001; 15(1):43-58. DOI: 10.1096/fj.99-1003rev. View

14.

BOZZA M, Bliss J, Dorner A, Trepicchio W . Interleukin-11 modulates Th1/Th2 cytokine production from activated CD4+ T cells. J Interferon Cytokine Res. 2001; 21(1):21-30. DOI: 10.1089/107999001459123. View

15.

Curti A, Ratta M, Corinti S, Girolomoni G, Ricci F, Tazzari P . Interleukin-11 induces Th2 polarization of human CD4(+) T cells. Blood. 2001; 97(9):2758-63. DOI: 10.1182/blood.v97.9.2758. View

16.

Hurst S, Wilkinson T, McLoughlin R, Jones S, Horiuchi S, Yamamoto N . Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation. Immunity. 2001; 14(6):705-14. DOI: 10.1016/s1074-7613(01)00151-0. View

17.

Moreland L, Gugliotti R, King K, Chase W, Weisman M, Greco T . Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis. Arthritis Res. 2001; 3(4):247-52. PMC: 34114. DOI: 10.1186/ar309. View

18.

Kerfoot S, Raharjo E, Ho M, Kaur J, Serirom S, McCafferty D . Exclusive neutrophil recruitment with oncostatin M in a human system. Am J Pathol. 2001; 159(4):1531-9. PMC: 1850489. DOI: 10.1016/S0002-9440(10)62538-2. View

19.

Katz Y, Nadiv O, Beer Y . Interleukin-17 enhances tumor necrosis factor alpha-induced synthesis of interleukins 1,6, and 8 in skin and synovial fibroblasts: a possible role as a "fine-tuning cytokine" in inflammation processes. Arthritis Rheum. 2001; 44(9):2176-84. DOI: 10.1002/1529-0131(200109)44:9<2176::aid-art371>3.0.co;2-4. View

20.

Yoshida H, Hamano S, Senaldi G, Covey T, Faggioni R, Mu S . WSX-1 is required for the initiation of Th1 responses and resistance to L. major infection. Immunity. 2001; 15(4):569-78. DOI: 10.1016/s1074-7613(01)00206-0. View