Faculty Collaboration Database

Intact Regulatory T-Cell Function but Defective Generation of IL-17A-Producing CD4+ T Cells in XIAP Deficiency. J Pediatr Gastroenterol Nutr 2016 Aug;63(2):218-25

Date

01/31/2016

Pubmed ID

26825770

DOI

10.1097/MPG.0000000000001122

Scopus ID

2-s2.0-84955587050 (requires institutional sign-in at Scopus site)

Abstract

OBJECTIVE: X-linked inhibitor of apoptosis (xIAP) deficiency is a primary immune deficiency disorder associated with hemophagocytic lymphohistiocytosis. About 17% of xIAP-deficient patients present with very early onset severe colitis with high mortality. We hypothesized that xIAP deficiency leads to defective generation and/or survival of T regulatory cells (Treg) through its involvement in transforming growth factor-β signaling.

METHODS AND RESULTS: We used a T-cell transfer model of chronic colitis and observed a mild increase in colitis severity induced by naïve CD4 T cells from xIAP mice compared with colitis induced by naïve CD4 T cells from WT mice. We did not observe any significant difference in the induction of Treg cells in these studies. We next tested whether xIAP is required for Treg cell function by co-transferring xIAP or WT Treg cells with naïve WT CD4 cells in this model. We demonstrate that XIAP-deficient Treg cells were able to prevent disease similarly to WT Treg cells. In these experiments we, however, found a significantly decreased percentage of IL-17A-producing CD4 T cells in mice receiving Tregs from xIAP mice.

CONCLUSIONS: xIAP appears dispensable for the generation of induced Treg cells as well as function of natural Treg cells. There appeared to be a role of xIAP in generation of IL-17-producing cells from either naïve CD4 T cells or Treg cells. Further research is needed to explore the role of xIAP in generation of IL-17-producing cells.

Author List

Gurram B, Hammelev E, Syverson G, Haribhai D, Yan K, Simpson P, Salzman N, Verbsky JW

Authors

Nita H. Salzman MD, PhD Center Director, Professor in the Pediatrics department at Medical College of Wisconsin
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
James Verbsky MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Chronic Disease
Colitis
Genetic Diseases, X-Linked
Inhibitor of Apoptosis Proteins
Interleukin-17
Lymphoproliferative Disorders
Mice
Mice, Inbred C57BL
Mice, Transgenic
Signal Transduction
T-Lymphocytes, Regulatory
Th17 Cells
Transforming Growth Factor beta