Th17 (T-helper-17) cytokine responses have been recently recognized as an important component for the protective immunity produced by vaccination. However, the mechanism by which immune adjuvants induce Th17 immunity has not been defined. We have developed a novel mucosal nanoemulsion (NE) adjuvant that produces a robust humoral and Th1 cellular immunity. Herein, we demonstrate that immunization with NE adjuvant induces a Th17 response to diverse antigens in both outbred and inbred mice. CD86 deficiency had a limited effect on the induction of IL-17, however, double CD80/CD86, CD40, and IL-6 (interleukin 6) mutant mice failed to produce Th17 immunity in response to NE adjuvant. Mice deficient in TLR2 and TLR4 (Toll-like receptors 2 and 4) had a diminished IL-17 response. Our data indicate that nasal mucosal immunization with NE adjuvant produces Th1 and Th17 immunity; that this process requires IL-6, CD40, and at least one of the CD80/CD86 molecules; and that the induction of TH17 is enhanced by the presence of TLR2 and TLR4 receptors. This unique approach to vaccination may have a significant role in protection against mucosal and intracellular pathogens.

These studies show that JAM-C and CD99 are aberrantly expressed in SSc skin. However, these adhesion molecules do not mediate myeloid cell-SSc skin adhesion. In contrast, we demonstrate an important role for ICAM-1 and VCAM-1 in the retention of myeloid cells in SSc skin, suggesting that targeting these molecules may be useful SSc therapies.

Objective-To investigate the role of Junctional adhesion molecule A (JAM-A) in the pathogenesis of systemic sclerosis (SSc).Methods-Biopsies from proximal and distal arm skin and serum were obtained from patients with SSc and normal (NL) volunteers. To determine the expression of JAM-A on SSc dermal fibroblasts and in SSc skin, cell surface ELISAs and immunohistology were performed. An ELISA was designed to determine the amount of soluble JAM-A (sJAM-A) in serum. Myeloid U937 cell-SSc dermal fibroblast and skin adhesion assays were performed to determine the role of JAM-A in myeloid cell adhesion.