Consistently, ICOS+ Tregs are involved in different immune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), sarcoidosis, with potential prognostic implications [20]: an elevated frequency of ICOS+ Tregs is directly correlated with SLE disease activity index scores and the serum antibody titer of anti-dsDNA [21]; moreover, a significantly larger proportion of ICOS+ Tregs was correlated to methotrexate unresponsiveness in RA patients [22]. This evidence concerns the gene ICOS and systemic lupus erythematosus.