Immunodeficiency and Autoimmune Enterocolopathy Linked to NFAT5 Haploinsufficiency

被引：26

作者：

Boland, Brigid S. ^{[1
,2
]}

Widjaja, Christella E. ^{[1
]}

Banno, Asoka ^{[1
]}

Zhang, Bing ^{[1
]}

Kim, Stephanie H. ^{[1
]}

Stoven, Samantha ^{[3
]}

Peterson, Michael R. ^{[4
]}

Jones, Marilyn C. ^{[5
,6
]}

Su, H. Irene ^{[7
]}

Crowe, Sheila E. ^{[1
]}

Bui, Jack D. ^{[8
]}

Ho, Samuel B. ^{[9
]}

Okugawa, Yoshinaga ^{[10
,11
]}

Goel, Ajay ^{[10
,11
]}

Marietta, Eric V. ^{[3
]}

Khosroheidari, Mahdieh ^{[12
]}

Jepsen, Kristen ^{[12
]}

Aramburu, Jose ^{[13
]}

Lopez-Rodriguez, Cristina ^{[13
]}

Sandborn, William J. ^{[1
,2
]}

Murray, Joseph A. ^{[3
]}

Harismendy, Olivier ^{[1
,14
]}

Chang, John T. ^{[1
,2
]}

机构：

[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Ctr Inflammatory Bowel Dis, La Jolla, CA 92093 USA

[3] Mayo Clin, Dept Med, Rochester, MN 55905 USA

[4] Western Washington Pathol & Multicare Hlth Syst, Tacoma, WA 98405 USA

[5] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA

[6] Univ Calif San Diego, Rady Childrens Hosp, La Jolla, CA 92093 USA

[7] Univ Calif San Diego, Dept Reprod Med, La Jolla, CA 92093 USA

[8] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA

[9] Vet Affairs Med Ctr, Dept Med, San Diego, CA 92161 USA

[10] Baylor Univ, Med Ctr, Baylor Res Inst, Ctr Gastrointestinal Res,Ctr Epigenet Canc Preven, Dallas, TX 75246 USA

[11] Baylor Univ, Med Ctr, Charles A Sammons Canc Ctr, Dallas, TX 75246 USA

[12] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA

[13] Pompeu Fabra Univ, Dept Expt & Hlth Sci, Immunol Unit, Barcelona 08003, Spain

[14] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA

来源：

JOURNAL OF IMMUNOLOGY | 2015年 / 194卷 / 06期

基金：

美国国家卫生研究院;

关键词：

INFLAMMATORY-BOWEL-DISEASE; TRANSCRIPTION FACTOR NFAT5; PATHOGENIC T(H)17 CELLS; OSMOTIC-STRESS; ULCERATIVE-COLITIS; UNIPARENTAL DISOMY; HYPERTONIC STRESS; GENE-EXPRESSION; ACTIVATION; PROTEIN;

D O I：

10.4049/jimmunol.1401463

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The link between autoimmune diseases and primary immunodeficiency syndromes has been increasingly appreciated. Immunologic evaluation of a young man with autoimmune enterocolopathy and unexplained infections revealed evidence of immunodeficiency, including IgG subclass deficiency, impaired Ag-induced lymphocyte proliferation, reduced cytokine production by CD8(+) T lymphocytes, and decreased numbers of NK cells. Genetic evaluation identified haploinsufficiency of NFAT5, a transcription factor regulating immune cell function and cellular adaptation to hyperosmotic stress, as a possible cause of this syndrome. Inhibition or deletion of NFAT5 in normal human and murine cells recapitulated several of the immune deficits identified in the patient. These results provide evidence of a primary immunodeficiency disorder associated with organ-specific autoimmunity linked to NFAT5 deficiency.

引用

页码：2551 / 2560

页数：10

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