Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein deficiency: modulatory role of regulatory B cells.

[wiskott-aldrich syndrome]

Patients deficient in the cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASp ) are predisposed to varied autoimmunity , suggesting it has an important controlling role in participating cells . IL -10 -producing regulatory B (Breg ) cells are emerging as important mediators of immunosuppressive activity . In experimental , antigen-induced arthritis WASp-deficient (WASp knockout [WAS KO ]) mice developed exacerbated disease associated with decreased Breg cells and regulatory T (Treg ) cells , but increased Th 17 cells in knee -draining LNs . Arthritic WAS KO mice showed increased serum levels of B-cell-activating factor , while their B cells were unresponsive in terms of B-cell-activating factor induced survival and IL -10 production . Adoptive transfer of WT Breg cells ameliorated arthritis in WAS KO recipients and restored a normal balance of Treg and Th 17 cells . Mice with B-cell-restricted WASp deficiency , however , did not develop exacerbated arthritis , despite exhibiting reduced Breg- and Treg-cell numbers during active disease , and Th 17 cells were not increased over equivalent WT levels . These findings support a contributory role for defective Breg cells in the development of WAS -related autoimmunity , but demonstrate that functional competence in other regulatory populations can be compensatory . A properly regulated cytoskeleton is therefore important for normal Breg-cell activity and complementation of defects in this lineage is likely to have important therapeutic benefits .

Diseases
Validation

Diseases presenting "however" symptom

adrenal incidentaloma

alexander disease

alpha-thalassemia

aromatase deficiency

benign recurrent intrahepatic cholestasis

cushing syndrome

dedifferentiated liposarcoma

dracunculiasis

dystrophic epidermolysis bullosa

esophageal carcinoma

focal myositis

heparin-induced thrombocytopenia

hodgkin lymphoma, classical

hydrocephalus with stenosis of the aqueduct of sylvius

junctional epidermolysis bullosa

krabbe disease

lamellar ichthyosis

megacystis-microcolon-intestinal hypoperistalsis syndrome

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

omenn syndrome

primary hyperoxaluria type 1

pyruvate dehydrogenase deficiency

sneddon syndrome

thoracic outlet syndrome

von hippel-lindau disease

wiskott-aldrich syndrome

x-linked adrenoleukodystrophy

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