Mobilization of natural killer cells inhibits development of collagen-induced arthritis.

• Although natural killer (NK) cells have been implicated in regulating immune responses, their ability to modulate disease development in autoimmune arthritis has not been analyzed. Here we investigate the contribution of NK cells to regulating collagen-induced arthritis, a well-characterized preclinical model of human rheumatoid arthritis. We find that the disease is induced by the combined action of two CD4(+) T helper (T(H)) subsets: follicular T(H) cells and T(H)17 cells. Both CD4(+) T(H) subsets are highly susceptible to lysis by NK cells after activation. Administration of antibody that activates NK cells through blockade of its inhibitory CD94/NKG2A receptor allows enhanced elimination of pathogenic follicular T(H) and T(H)17 cells and arrest of disease progression. These results suggest that antibody-dependent enhancement of NK activity may yield effective, previously undescribed therapeutic approaches to this autoimmune disorder.

Ämnesord

LANTBRUKSVETENSKAPER  -- Veterinärmedicin -- Klinisk vetenskap (hsv//swe)

AGRICULTURAL SCIENCES  -- Veterinary Science -- Clinical Science (hsv//eng)

Nyckelord

Animals

Arthritis

Experimental

etiology

prevention & control

Cell Communication

Killer Cells

Natural

physiology

Mice

Mice

Inbred C57BL

NK Cell Lectin-Like Receptor Subfamily C

physiology

NK Cell Lectin-Like Receptor Subfamily D

physiology

Th1 Cells

physiology

Th17 Cells

physiology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)