Annexin-A1 restricts Th17 cells and attenuates the severity of autoimmune disease

作者：Yazid Samia^*; Gardner Peter J; Carvalho Livia; Chu Colin J; Flower Roderick J; Solito Egle; Lee Richard W J; Ali Robin R; Dick Andrew D

来源：Journal of Autoimmunity, 2015, 58: 1-11.

DOI：10.1016/j.jaut.2014.12.004

• Annexin-A1
• Th17
• Autoimmune
• STAT3
• SOCS3
• Uveitis

Annexin-A1 (Anx-A1) is an endogenous anti-inflammatory molecule and while described as a repressor of innate immune responses, the role of Anx-A1 in adaptive immunity, and in particular in T helper (Th) cell responses, remains controversial. We have used a T-cell mediated mouse model of retinal autoimmune disease to unravel the role of Anx-A1 in the development of autoreactive Th cell responses and pathology. RBP1-20-immunized C57BL/6 Anx-A1(-/-) mice exhibit significantly enhanced retinal inflammation and pathology as a result of an uncontrolled proliferation and activation of Th17 cells. This is associated with a limited capacity to induce SOCS3, resulting in un-restricted phosphorylation of STAT3. RBP1-20-specific CD4(+) cells from immunized Anx-A1-/- animals generated high levels of Th17 cells-associated cytokines. Following disease induction, daily systemic administration of human recombinant Anx-A1 (hrAnx-A1), during the afferent phase of disease, restrained autoreactive CD4+ cell proliferation, reduced expression of pro-inflammatory cytokines IL-17, IFN-gamma and IL-6 and attenuated autoimmune retinal inflammatory disease. Furthermore, in man, Anx-A1 serum levels when measured in active uveitis patient sera were low and associated with the detection of IgM and IgG anti-Anx-A1 antibodies when compared to healthy individuals. This data supports Anx-A1 as an early and critical regulator of Th17 cell driven autoimmune diseases such as uveitis.

• 出版日期2015-4