18 / 20
Volume 4
Journal of Pediatric Care
ISSN: 2471-805X
Page 46
JOINT EVENT
Pediatric Critical Care 2018 &
World Pediatrics 2018
October 18- 20 , 2018
October 18- 20, 2018 Warsaw, Poland
&
6
th
International Conference on
25
th
World Pediatrics Conference
Pediatric Critical Care and Emergency Medicine
Effects of DOCK8 deficiency on IL-10 producing regulatory B cells
Jinqiu Jiang, Tao Qin, Xiaodong Zhao
and
Hua Wang
Chongqing Medical University, China
D
edicator of cytokinesis 8 (DOCK8) deficiencies are characterized by recurrent infections, increased serum IgE levels,
eosinophilia, and a significantly high risk of allergic and autoimmune manifestations. DOCK8 is a regulating factor of
actin cytoskeleton proteins involved in the development and differentiation of B cells. Regulatory B cells (Breg) are potent
negative regulators of antigen-specific inflammation and T-cell-dependent autoimmune diseases mainly through producing
inhibitory cytokine interleukin-10 (IL-10). The precise signaling mechanisms required for Breg functions remain unknown.
We sought to elucidate the effects of DOCK8 deficiency on Breg function in patients and DOCK8KO mice. DOCK8 deficient
patients (n=3) have decreased percentage of IL-10+CD19+regulatory B cells compared with healthy controls. In DOCK8KO
mice, the percentage and number of IL-10+CD19+regulatory B cells were reduced compared with WT mice after induced by
OVA. In DOCK8KO-WT bone marrow chimera mice, it showed the decreased number of Breg, but for DOCK8KO-μMT (B
cell deficient mice) bone marrow chimera mice showed the normal number of Breg. Adoptive transfer of DOCK8-/-CD4+
naïve T cells to CD4KO mice exhibited decreased Breg percentage. Finally, In vitro and in vivo administration of recombinant
IL-21could restores the percentage of Breg, it might be caused by LPS-driven, but not IL-21-driven, STAT3 phosphorylation
was defective in DOCK8KO mice. In conclusion, DOCK8 deficiency causes Breg intrinsic defect, as a result of abnormalities
of IL-21-producing CD4+ T cells in DOCK8 deficiency.
gincho@126.comJ Pediatr Care 2018, Volume 4
DOI: 10.21767/2471-805X-C4-015