To date in RA, four main environmental factors have been identified as greatly impacting the differentiation/activation of Mo-DCs: (i) the agonists of the AhR, (ii) the extra-cellular acidosis, (iii) the GM-CSF produced by synovial CD4+ T cells, and (iv) the synoviocytes and the synovial fluid. The gene discussed is CD4; the disease is rheumatoid arthritis.