Immunological aspects of endometriosis: a review.

Milena Králíčková, Vaclav Vetvicka, Václav Větvička
Annals of translational medicine · 2015 · vol. 3(11) , pp. 153 · doi:10.3978/j.issn.2305-5839.2015.06.08 · PMID:26244140 · PMC4499658 · W1519185389
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This review summarizes current knowledge on the immunological reactions involved in endometriosis, noting altered immune cell numbers and activities that may contribute to disease development.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-13 · read from full text ⓘ

This review synthesizes evidence on immunologic mechanisms in endometriosis, focusing on lymphocyte defects, macrophage dysfunction, autoimmunity hypotheses, inflammatory and cytokine profiles, and interactions with extracellular matrix and soluble mediators. It reports that nonspecific immunity markers can be unchanged, while T cell–mediated cytotoxicity to autologous endometrial cells is inhibited, NK cell activity is reduced, and these effects may involve serum factors such as cytokines and molecules like ICAM-1, alongside possible roles for Fas–FasL apoptosis pathways and KIR upregulation; key limitations are that the exact soluble factors and mechanisms are often unknown and some animal/model interpretations remain unproven. The paper further describes reduced macrophage phagocytic machinery linked to prostaglandin E2, complement-dominated chronic inflammation, and increased cytokines and growth factors in peritoneal fluid, with shifts in Th1/Th2 balance toward Th2 and increased Treg-related observations in certain models. This paper is centrally about endometriosis — a review of its immunological aspects, including lymphocyte, macrophage, and cytokine mechanisms relevant to disease pathogenesis.

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Abstract

Endometriosis is a common and serious illness affecting women in their reproductive years. Despite the ongoing interest and intensive research of this crippling disease, the cause remains unknown since its first description over 150 years ago. The origins and genesis of endometriosis, despite numerous hypotheses, are still unclear. One of the possible causes of the development of endometriosis might be the immune system, despite the fact that endometriosis is generally considered to be a steroid-sensitive disease. Numerous aspects of the immune system has been found changed, from the different number of activated macrophages to different subtypes of lymphocytes and their activities, suggesting involvement of immunity. On the other hand, it is possible that immunological changes around the endometriotic lesion are only secondary to the establishment of endometriosis. In this review, we will summarize the current knowledge of immunological reactions in endometriosis.
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Conclusions

Endometriosis is now considered to be a disease of both endocrine and immune dysregulation. This endocrine-immunologic axis underlines the complexity of this gynecologic disorder. However, recognition of the direct involvement of two major physiological mechanisms brings about a change of focus which might represent an interesting advance in the understanding of this disease and new focus for further research. Vast changes in activities of numerous cells involved in immune reactions might offer new therapeutic targets with Treg lymphocytes being the most promising.

Acknowledgements

Disclosure: The authors declare no conflict of interest.

References

- Von Rokitansky C. Uber Uterusdrusen-Neuerbildung in Uterus and Ovarilsarcomen Z Gesselschaft Aerzte Wien 1860;37:577-93. - Wood DH, Yochmowitz MG, Salmon YL, et al. Proton irradiation and endometriosis. Aviat Space Environ Med 1983;54:718-24. [PubMed] - Steele RW, Dmowski WP, Marmer DJ. Immunologic aspects of human endometriosis. Am J Reprod Immunol 1984;6:33-6. [PubMed] - Kanzaki H, Wang HS, Kariya M, et al. Suppression of natural killer cell activity by sera from patients with endometriosis. Am J Obstet Gynecol 1992;167:257-61. [PubMed] - Tanaka E, Sendo F, Kawagoe S, et al. Decreased natural killer cell activity in women with endometriosis. Gynecol Obstet Invest 1992;34:27-30. [PubMed] - Viganò P, Somigliana E, Di Blasio AM, et al. Suppression of natural killer cell function and production of soluble ICAM-1: endometrial stroma versus melanoma. Am J Reprod Immunol 2001;46:342-8. [PubMed] - Oosterlynck DJ, Meuleman C, Waer M, et al. Immunosuppressive activity of peritoneal fluid in women with endometriosis. Obstet Gynecol 1993;82:206-12. [PubMed] - Semino C, Semino A, Pietra G, et al. Role of major histocompatibility complex class I expression and natural killer-like T cells in the genetic control of endometriosis. Fertil Steril 1995;64:909-16. [PubMed] - Osuga Y, Koga K, Hirota Y, et al. Lymphocytes in endometriosis. Am J Reprod Immunol 2011;65:1-10. [PubMed] - Hornung D, Fujii E, Lim KH, et al. Histocompatibility leukocyte antigen-G is not expressed by endometriosis or endometrial tissue. Fertil Steril 2001;75:814-7. [PubMed] - Wu MY, Yang JH, Chao KH, et al. Increase in the expression of killer cell inhibitory receptors on peritoneal natural killer cells in women with endometriosis. Fertil Steril 2000;74:1187-91. [PubMed] - Chrobak A, Gmyrek GB, Sozański R, et al. The influence of extracellular matrix proteins on T-cell proliferation and apoptosis in women with endometriosis or uterine leiomyoma. Am J Reprod Immunol 2004;51:123-9. [PubMed] - Melioli G, Semino C, Semino A, et al. Recombinant interleukin-2 corrects in vitro the immunological defect of endometriosis. Am J Reprod Immunol 1993;30:218-27. [PubMed] - Ho HN, Wu MY, Chao KH, et al. Peritoneal interleukin-10 increases with decrease in activated CD4+ T lymphocytes in women with endometriosis. Hum Reprod 1997;12:2528-33. [PubMed] - Berbic M, Fraser IS. Regulatory T cells and other leukocytes in the pathogenesis of endometriosis. J Reprod Immunol 2011;88:149-55. [PubMed] - Budiu RA, Diaconu I, Chrissluis R, et al. A conditional mouse model for human MUC1-positive endometriosis shows the presence of anti-MUC1 antibodies and Foxp3+ regulatory T cells. Dis Model Mech 2009;2:593-603. [PubMed] - Vlad AM, Diaconu I, Gantt KR. MUC1 in endometriosis and ovarian cancer. Immunol Res 2006;36:229-36. [PubMed] - Wu MH, Shoji Y, Wu MC, et al. Suppression of matrix metalloproteinase-9 by prostaglandin E(2) in peritoneal macrophage is associated with severity of endometriosis. Am J Pathol 2005;167:1061-9. [PubMed] - de Villiers WJ, Fraser IP, Gordon S. Cytokine and growth factor regulation of macrophage scavenger receptor expression and function. Immunol Lett 1994;43:73-9. [PubMed] - Viganò P, Gaffuri B, Somigliana E, et al. Expression of intercellular adhesion molecule (ICAM)-1 mRNA and protein is enhanced in endometriosis versus endometrial stromal cells in culture. Mol Hum Reprod 1998;4:1150-6. [PubMed] - Dmowski WP, Steele RW, Baker GF. Deficient cellular immunity in endometriosis. Am J Obstet Gynecol 1981;141:377-83. [PubMed] - Maeda N, Izumiya C, Oguri H, et al. Aberrant expression of intercellular adhesion molecule-1 and killer inhibitory receptors induces immune tolerance in women with pelvic endometriosis. Fertil Steril 2002;77:679-83. [PubMed] - Capobianco A, Monno A, Cottone L, et al. Proangiogenic Tie2(+) macrophages infiltrate human and murine endometriotic lesions and dictate their growth in a mouse model of the disease. Am J Pathol 2011;179:2651-9. [PubMed] - Králíčková M, Vetvicka V. Endometriosis and ovarian cancer. World J Clin Oncol 2014;5:800-5. [PubMed] - Pasoto SG, Abrao MS, Viana VS, et al. Endometriosis and systemic lupus erythematosus: a comparative evaluation of clinical manifestations and serological autoimmune phenomena. Am J Reprod Immunol 2005;53:85-93. [PubMed] - Matorras R, Ocerin I, Unamuno M, et al. Prevalence of endometriosis in women with systemic lupus erythematosus and Sjogren's syndrome. Lupus 2007;16:736-40. [PubMed] - Taylor PV, Maloney MD, Campbell JM, et al. Autoreactivity in women with endometriosis. Br J Obstet Gynaecol 1991;98:680-4. [PubMed] - Garza D, Mathur S, Dowd MM, et al. Antigenic differences between the endometrium of women with and without endometriosis. J Reprod Med 1991;36:177-82. [PubMed] - Yeaman GR, Collins JE, Lang GA. Autoantibody responses to carbohydrate epitopes in endometriosis. Ann N Y Acad Sci 2002;955:174-82; discussion 199-200, 396-406. - Ulukus M, Cakmak H, Arici A. The role of endometrium in endometriosis. J Soc Gynecol Investig 2006;13:467-76. [PubMed] - Tanaka T, Umesaki N, Mizuno K, et al. Anti-endometrial IgM autoantibodies in endometriotic patients: a preliminary study. Clin Exp Obstet Gynecol 2000;27:133-7. [PubMed] - Vignali M, Infantino M, Matrone R, et al. Endometriosis: novel etiopathogenetic concepts and clinical perspectives. Fertil Steril 2002;78:665-78. [PubMed] - Nothnick WB, Curry TE, Vernon MW. Immunomodulation of rat endometriotic implant growth and protein production. Am J Reprod Immunol 1994;31:151-62. [PubMed] - Olovsson M. Immunological aspects of endometriosis: an update. Am J Reprod Immunol 2011;66 Suppl 1:101-4. [PubMed] - Suryawanshi S, Huang X, Elishaev E, et al. Complement pathway is frequently altered in endometriosis and endometriosis-associated ovarian cancer. Clin Cancer Res 2014;20:6163-74. [PubMed] - Giudice LC, Tazuke SI, Swiersz L. Status of current research on endometriosis. J Reprod Med 1998;43:252-62. [PubMed] - Iwabe T, Harada T, Tsudo T, et al. Pathogenetic significance of increased levels of interleukin-8 in the peritoneal fluid of patients with endometriosis. Fertil Steril 1998;69:924-30. [PubMed] - Bulun SE, Cheng YH, Pavone ME, et al. Estrogen receptor-beta, estrogen receptor-alpha, and progesterone resistance in endometriosis. Semin Reprod Med 2010;28:36-43. [PubMed] - Gilmore SM, Aksel S, Hoff C, et al. In vitro lymphocyte activity in women with endometriosis--an altered immune response? Fertil Steril 1992;58:1148-52. [PubMed] - Antsiferova YS, Sotnikova NY, Posiseeva LV, et al. Changes in the T-helper cytokine profile and in lymphocyte activation at the systemic and local levels in women with endometriosis. Fertil Steril 2005;84:1705-11. [PubMed] - Gmyrek GB, Sieradzka U, Goluda M, et al. Flow cytometric evaluation of intracellular cytokine synthesis in peripheral mononuclear cells of women with endometriosis. Immunol Invest 2008;37:43-61. [PubMed] - Ali AF, Fateen B, Ezzet A, et al. Laparoscopic intraperitoneal injection of human interferon-α2b in the treatment of pelvic endometriosis: a new modality. Obstet Gynecol 2000;95:47S-8S. - D'Antonio M, Martelli F, Peano S, et al. Ability of recombinant human TNF binding protein-1 (r-hTBP-1) to inhibit the development of experimentally-induced endometriosis in rats. J Reprod Immunol 2000;48:81-98. [PubMed] - Bedaiwy MA, Falcone T, Sharma RK, et al. Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod 2002;17:426-31. [PubMed] - Kao AP, Wang KH, Long CY, et al. Interleukin-1β induces cyclooxygenase-2 expression and promotes the invasive ability of human mesenchymal stem cells derived from ovarian endometrioma. Fertil Steril 2011;96:678-84. [PubMed] - Herington JL, Bruner-Tran KL, Lucas JA, et al. Immune interactions in endometriosis. Expert Rev Clin Immunol 2011;7:611-26. [PubMed]

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