Cutting Edge: Commensal Microbiota Has Disparate Effects on Manifestations of Polyglandular Autoimmune Inflammation.
Polyglandular autoimmune inflammation accompanies type 1 diabetes (T1D) in NOD mice, affecting organs like thyroid and salivary glands. Although commensals are not required for T1D progression, germ-free (GF) mice had a very low degree of sialitis, which was restored by colonization with select microbial lineages. Moreover, unlike T1D, which is blocked in mice lacking MyD88 signaling adaptor under conventional, but not GF, housing conditions, sialitis did not develop in MyD88(-/-) GF mice. Thus, microbes and MyD88-dependent signaling are critical for sialitis development. The severity of sialitis did not correlate with the degree of insulitis in the same animal and was less sensitive to a T1D-reducing diet, but it was similar to T1D with regard to microbiota-dependent sexual dimorphism. The unexpected distinction in requirements for the microbiota for different autoimmune pathologies within the same organism is crucial for understanding the nature of microbial involvement in complex autoimmune disorders, including human autoimmune polyglandular syndromes.
Department of Pathology, The University of Chicago, Chicago, IL 60637; Committee on Immunology, The University of Chicago, Chicago, IL 60637; Faculty of Health and Medical Sciences, University of Copenhagen, 1871 Frederiksberg C, Denmark; and.
Camilla H F
CH
Hansen
Department of Pathology, The University of Chicago, Chicago, IL 60637; Committee on Microbiology, The University of Chicago, Chicago, IL 60637.
Leonid A
0000-0001-5078-493X
LA
Yurkovetskiy
Department of Pathology, The University of Chicago, Chicago, IL 60637; Committee on Immunology, The University of Chicago, Chicago, IL 60637; Committee on Microbiology, The University of Chicago, Chicago, IL 60637 achervon@bsd.uchicago.edu.
Alexander V
0000-0001-7547-871X
AV
Chervonsky
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000382:microbiology*; D004195:Disease Models, Animal; D005260:Female; D005856:Germ-Free Life; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D064307:Microbiota / Q000502:physiology*; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D016884:Polyendocrinopathies, Autoimmune / Q000382:microbiology*; D012727:Sex Characteristics; D012793:Sialadenitis / Q000382:microbiology*
D053594:Myeloid Differentiation Factor 88