Cutting Edge: Commensal Microbiota Has Disparate Effects on Manifestations of Polyglandular Autoimmune Inflammation

TY - JOUR

T1 - Cutting Edge

T2 - Commensal Microbiota Has Disparate Effects on Manifestations of Polyglandular Autoimmune Inflammation

AU - Hansen, Camilla H F

AU - Yurkovetskiy, Leonid A

AU - Chervonsky, Alexander V

N1 - Copyright © 2016 by The American Association of Immunologists, Inc.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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 inMyD882/2 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.

AB - 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 inMyD882/2 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.

KW - Journal Article

U2 - 10.4049/jimmunol.1502465

DO - 10.4049/jimmunol.1502465

M3 - Journal article

C2 - 27324130

SN - 0022-1767

VL - 197

SP - 701

EP - 705

JO - Journal of Immunology

JF - Journal of Immunology

IS - 3

ER -