TY - JOUR
T1 - CD4+ T Cell Defects in a Mulibrey Patient With Specific TRIM37 Mutations
AU - Bruzzaniti, Sara
AU - Cirillo, Emilia
AU - Prencipe, Rosaria
AU - Giardino, Giuliana
AU - Lepore, Maria Teresa
AU - Garziano, Federica
AU - Perna, Francesco
AU - Procaccini, Claudio
AU - Mascolo, Luigi
AU - Pagano, Cristina
AU - Fattorusso, Valentina
AU - Mozzillo, Enza
AU - Bifulco, Maurizio
AU - Matarese, Giuseppe
AU - Franzese, Adriana
AU - Pignata, Claudio
AU - Galgani, Mario
N1 - Funding Information:
We thank Mr. A. d'Andrea and all members of the IEOS-CNR for technical support. We also thank all members of the Treg cell lab for help in the realization of the present study. Funding. This paper was supported by grants from the Juvenile Diabetes Research Foundation (JDRF n. 2-SRA-2018-479-S-B) and the National Multiple Sclerosis Society (NMSS n. PP-1804-30725) to MG; Fondazione Italiana Sclerosi Multipla (FISM n. 2016/R/18 and FISM n. 2018/S/5), and Progetti di Rilevante Interesse Nazionale (PRIN, 2017 K55HLC 001) to GM; the Italian Ministry of Health grants (n. GR-2016-02363749 and n. GR-2018-12366154) to CPr.
Publisher Copyright:
© Copyright © 2020 Bruzzaniti, Cirillo, Prencipe, Giardino, Lepore, Garziano, Perna, Procaccini, Mascolo, Pagano, Fattorusso, Mozzillo, Bifulco, Matarese, Franzese, Pignata and Galgani.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/9/18
Y1 - 2020/9/18
N2 - Mulibrey (muscle-liver-brain-eye) syndrome (MUL) is an autosomal recessive disorder caused by mutations in the TRIpartite motif (TRIM)37 gene, encoding for TRIM37 a member of the TRIM E3 ubiquitin ligase protein family. MUL patients are characterized by growth retardation, dysmorphic features, and a wide range of abnormalities affecting different organs. However, T-cell abnormalities have not been observed in MUL subjects, to date. Here we described the immunological features of a MUL child carrying recently identified TRIM37 mutations, a 17q22 deletion of maternal origin combined with a TRIM37 variant of paternal origin. Here we found quantitative and functional defects in CD4+ T cells from this MUL case. Low levels of TRIM37 protein were specifically detected in CD4+ T cells of MUL patient and associated with their altered proliferation and cytokine production. Of note, both CD4+ and CD8+ T lymphocytes of MUL child displayed an effector memory phenotype compared with healthy children. This clinical case research highlighted the possible role of TRIM37 in the control of immune cell number and function, especially in CD4+ T cells. Finally, this study may contribute to the novel mechanistic studies aim of identifying, in depth, the role of the TRIM37 protein in the immune system.
AB - Mulibrey (muscle-liver-brain-eye) syndrome (MUL) is an autosomal recessive disorder caused by mutations in the TRIpartite motif (TRIM)37 gene, encoding for TRIM37 a member of the TRIM E3 ubiquitin ligase protein family. MUL patients are characterized by growth retardation, dysmorphic features, and a wide range of abnormalities affecting different organs. However, T-cell abnormalities have not been observed in MUL subjects, to date. Here we described the immunological features of a MUL child carrying recently identified TRIM37 mutations, a 17q22 deletion of maternal origin combined with a TRIM37 variant of paternal origin. Here we found quantitative and functional defects in CD4+ T cells from this MUL case. Low levels of TRIM37 protein were specifically detected in CD4+ T cells of MUL patient and associated with their altered proliferation and cytokine production. Of note, both CD4+ and CD8+ T lymphocytes of MUL child displayed an effector memory phenotype compared with healthy children. This clinical case research highlighted the possible role of TRIM37 in the control of immune cell number and function, especially in CD4+ T cells. Finally, this study may contribute to the novel mechanistic studies aim of identifying, in depth, the role of the TRIM37 protein in the immune system.
KW - CD4 T cells
KW - immune response
KW - immunological defects
KW - Mulibrey syndrome
KW - TRIM37
UR - http://www.scopus.com/inward/record.url?scp=85091920781&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85091920781&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2020.01742
DO - 10.3389/fimmu.2020.01742
M3 - Article
C2 - 33042106
AN - SCOPUS:85091920781
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 1742
ER -