Cutting edge: Increased IL-17-secreting T cells in children with new-onset type 1 diabetes.
CD4(+)FOXP3(+) regulatory T cells are essential for immune tolerance, and murine studies suggest that their dysfunction can lead to type 1 diabetes (T1D). Human studies assessing regulatory T cell dysfunction in T1D have relied on analysis of FOXP3-expressing cells. Recently, distinct subsets of CD4(+)FOXP3(+) T cells with differing function were identified. Notably, CD45RA(-)CD25(int)FOXP3(low) T cells lack suppressive function and secrete the proinflammatory cytokine IL-17. Therefore, we evaluated whether the relative fractions of CD4(+)FOXP3(+) subsets are altered in new-onset T1D subjects. We report that children with new-onset T1D have an increased proportion of CD45RA(-)CD25(int)FOXP3(low) cells that are not suppressive and secrete significantly more IL-17 than other FOXP3(+) subsets. Moreover, these T1D subjects had a higher proportion of both CD4(+) and CD8(+) T cells that secrete IL-17. The bias toward IL-17-secreting T cells in T1D suggests a role for this proinflammatory cytokine in the pathogenesis of disease.
Marwaha
Ashish K
AK
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Crome
Sarah Q
SQ
Panagiotopoulos
Constadina
C
Berg
Kyra B
KB
Qin
Huilian
H
Ouyang
Qin
Q
Xu
Lixin
L
Priatel
John J
JJ
Levings
Megan K
MK
Tan
Rusung
R
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D017493:Leukocyte Common Antigens