دورية أكاديمية
أعرض في EDS

Familial hemophagocytic lymphohistiocytosis hepatitis is mediated by IFN-γ in a predominantly hepatic-intrinsic manner.

التفاصيل البيبلوغرافية
العنوان: Familial hemophagocytic lymphohistiocytosis hepatitis is mediated by IFN-γ in a predominantly hepatic-intrinsic manner.
المؤلفون: Diamond T; Division of Gastroenterology Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America., Burn TN; Perlman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States of America., Nishiguchi MA; Perlman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States of America., Minichino D; Perlman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States of America., Chase J; Division of Rheumatology, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America., Chu N; Division of Rheumatology, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America., Kreiger PA; Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America., Behrens EM; Division of Rheumatology, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
المصدر: PloS one [PLoS One] 2022 Jun 07; Vol. 17 (6), pp. e0269553. Date of Electronic Publication: 2022 Jun 07 (Print Publication: 2022).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Hepatitis*/pathology , Lymphohistiocytosis, Hemophagocytic*/genetics , Lymphohistiocytosis, Hemophagocytic*/pathology, Animals ; CD8-Positive T-Lymphocytes ; Interferon-gamma/metabolism ; Mice
مستخلص: Interferon gamma (IFN-γ) is the main cytokine driving organ dysfunction in Familial Hemophagocytic Lymphohistiocytosis (FHL). Blockade of IFN-γ pathway ameliorates FHL hepatitis, both in animal models and in humans with FHL. Hepatocytes are known to express IFN-γ receptor (IFN-γ-R). However, whether IFN-γ induced hepatitis in FHL is a lymphocyte or liver intrinsic response to the cytokine has yet to be elucidated. Using a IFNgR-/- bone marrow chimeric model, this study showed that non-hematopoietic IFN-γ response is critical for development of FHL hepatitis in LCMV-infected Prf1-/- mice. Lack of hepatic IFN-γ responsiveness results in reduced hepatitis as measured by hepatomegaly, alanine aminotransferase (ALT) levels and abrogated histologic endothelial inflammation. In addition, IFN-γ non-hematopoietic response was critical in activation of lymphocytes by soluble interleukin 2 receptor (sIL-2r) and recruitment of CD8+ effector T lymphocytes (CD8+ CD44hi CD62Llo) (Teff) and inflammatory monocytes. Lastly, non-hematopoietic IFN-γ response results in increased hepatic transcription of type 1 immune response and oxidative stress response pathways, while decreasing transcription of genes involved in extracellular matrix (ECM) production. In summary, these findings demonstrate that there is a hepatic transcriptional response to IFN-γ, likely critical in the pathogenesis of FHL hepatitis and hepatic specific responses could be a therapeutic target in this disorder.
Competing Interests: Conflict of Interest: All authors have no conflict of interest relevant to this manuscript All animal studies were performed with approval from The Children’s Hospital of Philadelphia Institutional Animal Care and Use Committee.
References: J Immunol. 2002 Dec 15;169(12):7111-8. (PMID: 12471148)
Liver Transpl. 2016 Sep;22(9):1245-53. (PMID: 27216884)
Nucleic Acids Res. 2015 Apr 20;43(7):e47. (PMID: 25605792)
Comp Med. 2015 Apr;65(2):96-113. (PMID: 25926395)
Cytokine Growth Factor Rev. 2011 Feb;22(1):35-43. (PMID: 21334249)
J Hepatol. 2007 Feb;46(2):295-303. (PMID: 17125875)
Bioinformatics. 2010 Jan 1;26(1):139-40. (PMID: 19910308)
Transl Res. 2017 Feb;180:37-52.e2. (PMID: 27559680)
Arthritis Rheumatol. 2019 Jan;71(1):161-168. (PMID: 30073799)
Pediatr Clin North Am. 2012 Apr;59(2):329-44. (PMID: 22560573)
N Engl J Med. 2020 May 7;382(19):1811-1822. (PMID: 32374962)
Hepatology. 2006 Dec;44(6):1441-51. (PMID: 17133483)
Am J Surg Pathol. 2010 Jun;34(6):852-67. (PMID: 20442642)
World J Hepatol. 2015 Dec 18;7(29):2880-9. (PMID: 26692473)
Biochem Biophys Res Commun. 1999 Apr 21;257(3):672-7. (PMID: 10208842)
Cell Mol Immunol. 2016 May;13(3):347-53. (PMID: 27041636)
Gastroenterology. 2006 Feb;130(2):435-52. (PMID: 16472598)
Hepatology. 2014 Oct;60(4):1356-66. (PMID: 24623351)
Gastroenterology. 1996 Aug;111(2):462-71. (PMID: 8690213)
J Pediatr Gastroenterol Nutr. 2020 Dec;71(6):713-719. (PMID: 32796431)
EMBO Mol Med. 2009 May;1(2):112-24. (PMID: 20049711)
Proc Natl Acad Sci U S A. 2018 Jan 2;115(1):180-185. (PMID: 29255036)
Cell Mol Immunol. 2021 Jan;18(1):18-37. (PMID: 33203939)
Cancer Chemother Pharmacol. 2021 Mar;87(3):295-309. (PMID: 33112969)
PLoS One. 2019 Dec 17;14(12):e0226043. (PMID: 31846457)
Clin Gastroenterol Hepatol. 2005 Aug;3(8):819-28. (PMID: 16234012)
Blood. 2019 Nov 21;134(21):1783-1786. (PMID: 31537529)
J Leukoc Biol. 2021 May;109(5):943-952. (PMID: 33899953)
Nat Biotechnol. 2016 May;34(5):525-7. (PMID: 27043002)
J Clin Immunol. 2020 Jul;40(5):699-707. (PMID: 32447592)
Arthritis Rheumatol. 2020 Feb;72(2):335-347. (PMID: 31400073)
Hepatol Commun. 2019 Apr 22;3(6):730-743. (PMID: 31168508)
PLoS One. 2014 Oct 13;9(10):e110162. (PMID: 25310404)
Front Immunol. 2020 May 08;11:808. (PMID: 32457750)
J Allergy Clin Immunol. 2018 Apr;141(4):1439-1449. (PMID: 28807602)
F1000Res. 2015 Dec 30;4:1521. (PMID: 26925227)
Haematologica. 2015 Jul;100(7):978-88. (PMID: 26022711)
J Immunol. 2008 May 15;180(10):6713-24. (PMID: 18453591)
J Clin Invest. 2016 Nov 1;126(11):4346-4360. (PMID: 27756058)
Gastroenterology. 2011 Mar;140(3):830-9. (PMID: 20854821)
Blood. 2016 Jan 28;127(4):426-35. (PMID: 26518437)
Blood. 2004 Aug 1;104(3):735-43. (PMID: 15069016)
Hepatol Commun. 2021 May 06;5(8):1373-1384. (PMID: 34430782)
Front Immunol. 2018 Nov 20;9:2642. (PMID: 30515155)
Arthritis Rheumatol. 2021 May;73(5):885-895. (PMID: 33191652)
Cytokine Growth Factor Rev. 2015 Jun;26(3):263-80. (PMID: 25466631)
J Pediatr. 2014 Feb;164(2):407-9. (PMID: 24315507)
Mol Immunol. 2020 Jul;123:106-115. (PMID: 32485469)
Am Surg. 2009 Jan;75(1):49-54. (PMID: 19213397)
معلومات مُعتمدة: R01 AI121250 United States AI NIAID NIH HHS; S06 GM008216 United States GM NIGMS NIH HHS; T32 DK101371 United States DK NIDDK NIH HHS; T32 GM008216 United States GM NIGMS NIH HHS
المشرفين على المادة: 82115-62-6 (Interferon-gamma)
تواريخ الأحداث: Date Created: 20220607 Date Completed: 20220609 Latest Revision: 20240514
رمز التحديث: 20240514
مُعرف محوري في PubMed: PMC9173616
DOI: 10.1371/journal.pone.0269553
PMID: 35671274
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0269553