B6 mice have the wrong MHC haplotype for collagen-induced arthritis --> resistant to developing arthritis upon collagen challenge. 

CD11bko B6 mice do develop arthritis upon collagen challenge. *How does severity compare to e.g. Balb/c mice?

Elevated Th17 response in challenged CD11bko mice: - increased %CD4 producing IL-17 (PMA/iono stimulation ex vivo) - increased IL-17 in ‘joint cell lysates’ (synovium?) - increased serum IL-6

Reduced immune regulation: - decreased IL-10 producing B cells (splenocytes, LPS stimulation) - decreased Tregs in draining lymph nodes

IL-6 receptor blocking Ab (15A7) - in vitro: reduced Th17 differentiation (presumed IL-6/IL-17 positive feedback loop) - in vivo: reduced arthritis severity, reduced Th17 cell, increased %Tregs to WT levels

CD11b+ DC clonal line adoptive transfer - reduced arthritis severity - cells shown to produce less IL-6 upon CD11b binding with antibody

FIg. 4

INTERESTING:

Role for DC-derived IL-6 and a proposed mechanism to control this production through CD11b (albeit very preliminary).

Problems:

* Why would ADDING CD11b+ DCs which produce LESS IL-6 affect the pre-existing CD11b- DCs as a whole? Does it change serum IL-6 or IL-17?

* Does addition of CD11b into the system affect Treg numbers? Is it just a homeostatic reciprocal relationship with Th17, a negative feedback to IL-6, or does CD11b affect Treg expansion directly?

* What is the purpose of CD11b expression on other (non-DC) myeloid cells? How do they affect inflammation?

* How would anti-CD11b antibodies affect disease progression in non-resistant mice? Can we stimulate Th-17 suppression by binding CD11b?