B lymphocytes inactivation by Ibrutinib limits endometriosis progression in mice

Imagem de Miniatura
Arquivos
art_RICCIO_B_lymphocytes_inactivation_by_Ibrutinib_limits_endometriosis_progression_2019.PDF (38.5 MB)
Citações na Scopus
21
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
OXFORD UNIV PRESS
Autores
JELJELI, M.
SANTULLI, P.
CHOUZENOUX, S.
DORIDOT, L.
NICCO, C.
REIS, F. M.
CHAPRON, C.
BATTEUX, F.
Citação
HUMAN REPRODUCTION, v.34, n.7, p.1225-1234, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
STUDY QUESTION: What are the effects of B lymphocyte inactivation or depletion on the progression of endometriosis? SUMMARY ANSWER: Skewing activated B cells toward regulatory B cells (Bregs) by Bruton's tyrosine kinase (Btk) inhibition using Ibrutinib prevents endometriosis progression in mice while B cell depletion using an anti-CD20 antibody has no effect. WHAT IS KNOWN ALREADY: A polyclonal activation of B cells and the presence of anti-endometrial autoanti bodies have been described in a large proportion of women with endometriosis though their exact role in the disease mechanisms remains unclear. STUDY DESIGN, SIZE, DURATION: This study included comparison of endometriosis progression for 21 days in control mice versus animals treated with the anti-CD20 depleting antibody or with the Btk inhibitor Ibrutinib that prevents B cell activation. PARTICIPANTS/MATERIALS, SETTING, METHODS: After syngeneic endometrial transplantation, murine endometriotic lesions were compared between treated and control mice using volume, weight, ultrasonography, histology and target genes expression in lesions. Phenotyping of activated and regulatory B cells, T lymphocytes and macrophages was performed by flow cytometry on isolated spleen and peritoneal cells. Cytokines were assayed by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE: Btk inhibitor Ibrutinib prevented lesion growth, reduced mRNA expression of cyclooxygenase-2, alpha smooth muscle actin and type I collagen in the lesions and skewed activated B cells toward Bregs in the spleen and peritoneal cavity of mice with endometriosis. In addition, the number of M2 macrophages decreased in the peritoneal cavity of Ibrutinibtreated mice compared to anti-CD20 and control mice. Depletion of B cells using an anti-CD20 antibody had no effect on activity and growth of endometriotic lesions and neither on the macrophages, compared to control mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: It is still unclear whether B cell depletion by the anti-CD20 or inactivation by Ibrutinib can prevent establishment and/or progression of endometriosis in humans. WIDER IMPLICATIONS OF THE FINDINGS: Further investigation may contribute to clarifying the role of B cell subsets in human endometriosis.
Palavras-chave
endometriosis, B lymphocytes, Ibrutinib, Btk inhibitor, anti-CD20, regulatory B cells, macrophages, mice
URI
https://observatorio.fm.usp.br/handle/OPI/34057
Referências
  1. Bacci M, 2009, AM J PATHOL, V175, P547, DOI 10.2353/ajpath.2009.081011
  2. Beste MT, 2014, SCI TRANSL MED, V6, DOI 10.1126/scitranslmed.3007988
  3. Chen P, 2016, J OBSTET GYNAECOL RE, V42, P669, DOI 10.1111/jog.12957
  4. Riccio LDC, 2018, BEST PRACT RES CL OB, V50, P39, DOI 10.1016/j.bpobgyn.2018.01.010
  5. Corneth OBJ, 2016, J IMMUNOL, V197, P58, DOI 10.4049/jimmunol.1600208
  6. D'Hooghe TM, 2002, HUM REPROD UPDATE, V8, P84, DOI 10.1093/humupd/8.1.84
  7. de Gorter DJJ, 2007, IMMUNITY, V26, P93, DOI 10.1016/j.immuni.2006.11.012
  8. Dubovsky JA, 2014, J CLIN INVEST, V124, P4867, DOI 10.1172/JCI75328
  9. Dubovsky JA, 2013, BLOOD, V122, P2539, DOI 10.1182/blood-2013-06-507947
  10. Edwards JCW, 2004, NEW ENGL J MED, V350, P2572, DOI 10.1056/NEJMoa032534
  11. FERNANDEZSHAW S, 1993, HUM REPROD, V8, P310, DOI 10.1093/oxfordjournals.humrep.a138042
  12. Giudice LC, 2004, LANCET, V364, P1789, DOI 10.1016/S0140-6736(04)17403-5
  13. Gogacz M, 2016, J REPROD IMMUNOL, V117, P39, DOI 10.1016/j.jri.2016.04.289
  14. Gonzalez-Foruria I, 2017, MOL HUM REPROD, V23, P488, DOI 10.1093/molehr/gax028
  15. Harrison C, 2012, NAT REV DRUG DISCOV, V11, P96, DOI 10.1038/nrd3656
  16. Herman SEM, 2011, BLOOD, V117, P6287, DOI 10.1182/blood-2011-01-328484
  17. Honigberg LA, 2010, P NATL ACAD SCI USA, V107, P13075, DOI 10.1073/pnas.1004594107
  18. Jin GH, 2013, J ALLERGY CLIN IMMUN, V131, P1674, DOI 10.1016/j.jaci.2013.01.044
  19. Kil LP, 2012, BLOOD, V119, P3744, DOI 10.1182/blood-2011-12-397919
  20. Kokhaei P, 2016, J DRUG TARGET, V24, P373, DOI 10.3109/1061186X.2015.1086357
  21. Kuehn HS, 2010, J CELL SCI, V123, P2576, DOI 10.1242/jcs.071043
  22. Long MX, 2017, J CLIN INVEST, V127, P3052, DOI 10.1172/JCI89756
  23. Lundy SK, 2005, INFLAMM RES, V54, P514, DOI 10.1007/s00011-005-1387-0
  24. Marcellin L, 2017, FREE RADICAL BIO MED, V110, P1, DOI 10.1016/j.freeradbiomed.2017.04.362
  25. Matarese G, 2003, TRENDS MOL MED, V9, P223, DOI 10.1016/S1471-4914(03)00051-0
  26. Ni Gabhann J, 2014, PLOS ONE, V9, DOI 10.1371/JOURNAL.PONE.0085834
  27. Riccio LGC, 2017, J REPROD IMMUNOL, V123, P29, DOI 10.1016/j.jri.2017.09.001
  28. Rosser EC, 2015, IMMUNITY, V42, P607, DOI 10.1016/j.immuni.2015.04.005
  29. Sampson JA, 1927, AM J OBSTET GYNECOL, V14, P422, DOI 10.1016/S0002-9378(15)30003-X
  30. Santulli P, 2016, EXPERT OPIN THER TAR, V20, P1017, DOI 10.1080/14728222.2016.1180367
  31. Santulli P, 2015, EXPERT OPIN THER TAR, V19, P1465, DOI 10.1517/14728222.2015.1090974
  32. Schwager K, 2011, HUM REPROD, V26, P2344, DOI 10.1093/humrep/der195
  33. TOMAYKO MM, 1989, CANCER CHEMOTH PHARM, V24, P148, DOI 10.1007/BF00300234
  34. Vigano P, 2018, HUM REPROD, V33, P347, DOI 10.1093/humrep/dex354
  35. Weber ANR, 2017, FRONT IMMUNOL, V8, DOI 10.3389/fimmu.2017.01454
  36. WILD RA, 1985, AM J REPROD IM MIC, V8, P84
  37. Woyach JA, 2012, BLOOD, V120, P1175, DOI 10.1182/blood-2012-02-362624

Coleções
Artigos e Materiais de Revistas Científicas - FM/MOG
Artigos e Materiais de Revistas Científicas - LIM/58