TY - JOUR
T1 - A mouse model of HIES reveals pro- And anti-inflammatory functions of STAT3
AU - Steward-Tharp, Scott M.
AU - Laurence, Arian
AU - Kanno, Yuka
AU - Kotlyar, Alex
AU - Villarino, Alejandro V.
AU - Sciume, Giuseppe
AU - Kuchen, Stefan
AU - Resch, Wolfgang
AU - Wohlfert, Elizabeth A.
AU - Jiang, Kan
AU - Hirahara, Kiyoshi
AU - Vahedi, Golnaz
AU - Sun, Hong Wei
AU - Feigenbaum, Lionel
AU - Milner, Joshua D.
AU - Holland, Steven M.
AU - Casellas, Rafael
AU - Powrie, Fiona
AU - O'Shea, John J.
PY - 2014/5/8
Y1 - 2014/5/8
N2 - Mutations of STAT3 underlie the autosomal dominant form of hyperimmunoglobulin E syndrome (HIES). STAT3 has critical roles in immune cells and thus, hematopoietic stem cell transplantation (HSCT), might be a reasonable therapeutic strategy in this disease. However, STAT3 also has critical functions in nonhematopoietic cells and dissecting the protean roles of STAT3 is limited by the lethality associated with germline deletion of Stat3. Thus, predicting the efficacy of HSCT for HIES is difficult. To begin to dissect the importance of STAT3 in hematopoietic and nonhematopoietic cells as it relates to HIES, we generated a mouse model of this disease. We found that these transgenic mice recapitulate multiple aspects of HIES, including elevated serum IgE and failure to generate Th17 cells. Wefound that these mice were susceptible to bacterial infection that was partially corrected by HSCT using wild-type bone marrow, emphasizing the role played by the epithelium in the pathophysiology of HIES.
AB - Mutations of STAT3 underlie the autosomal dominant form of hyperimmunoglobulin E syndrome (HIES). STAT3 has critical roles in immune cells and thus, hematopoietic stem cell transplantation (HSCT), might be a reasonable therapeutic strategy in this disease. However, STAT3 also has critical functions in nonhematopoietic cells and dissecting the protean roles of STAT3 is limited by the lethality associated with germline deletion of Stat3. Thus, predicting the efficacy of HSCT for HIES is difficult. To begin to dissect the importance of STAT3 in hematopoietic and nonhematopoietic cells as it relates to HIES, we generated a mouse model of this disease. We found that these transgenic mice recapitulate multiple aspects of HIES, including elevated serum IgE and failure to generate Th17 cells. Wefound that these mice were susceptible to bacterial infection that was partially corrected by HSCT using wild-type bone marrow, emphasizing the role played by the epithelium in the pathophysiology of HIES.
UR - https://www.scopus.com/pages/publications/84900428801
U2 - 10.1182/blood-2013-09-523167
DO - 10.1182/blood-2013-09-523167
M3 - Article
C2 - 24632714
AN - SCOPUS:84900428801
SN - 0006-4971
VL - 123
SP - 2978
EP - 2987
JO - Blood
JF - Blood
IS - 19
ER -