TLR4 and systemic sclerosis: Immunomodulatory molecules implicated in driving aberrant TLR signalling in SSc include viruses such as cytomegalovirus, parvovirus B19, Epstein-Barr virus and the environmental fungus Rhodotorula glutinis33, 34, as well as autoantibodies capable of binding to, and activating, TLR4 (ref. 35).