Essential role for CD103+ cells in the pathogenesis of spondyloarthritides

The clinical features of spondyloarthritides include extraarticular manifestations involving the skin, eyes, and gastrointestinal tract. At these sites, a membrane integrin can be acquired by virtue of the presence of CD4+ T cells and specific dendritic cells and correlates with a regulatory behavior of these cells. This membrane integrin conjugates the beta7 subunit and the alphaE subunit, also known as CD103. CD103 expression requires high levels of TGF-beta and retinoic acid; in addition, expression of CD103 by T cells requires antigen recognition. Whether CD103 is found in the entheses has not yet been investigated. CD103 is expressed at high levels in the skin, eyes, and bowel but it is found in only very low levels in the bloodstream. CD8+ CD103+ T cells differ markedly from other CD103+ cells in that they are resident cells with no tendency to migrate and usually exert predominantly cytotoxic functions as opposed to regulatory functions. Several bacteria, such as Salmonella, can become dormant within the mucous membranes and/or their lymph nodes, where they use CD103+ dendritic cells and CD4+ CD103+ regulatory T cells (Tregs) to evade the immune response. This phenomenon could be studied in other tissues targeted by spondyloarthritides, where dormant microorganisms can migrate by using M2 macrophages as Trojan horses, since M2 macrophages express the CD103 ligand E-cadherin. Microorganism peptide recognition by CD8+ CD103+ T cells (which are overrepresented in psoriasis and joint fluid in some forms of spondyloarthritis) induces an inflammatory response that may be sufficient to transiently reverse the regulatory function of the CD103+ dendritic cells and CD4+ CD103+ T cells during disease flares. The sensitivity of these diseases to retinoids further supports a pathogenic role for transient CD103+ cell failure.