Cutting Edge: Increased IL-17–Secreting T Cells in Children with New-Onset Type 1 Diabetes
- Ashish K. Marwaha*†,
- Sarah Q. Crome‡§,
- Constadina Panagiotopoulos†¶,
- Kyra B. Berg‡§,
- Huilian Qin*†,
- Qin Ouyang*†,
- Lixin Xu*†,
- John J. Priatel*†,
- Megan K. Levingsठand
- Rusung Tan*†
- *Department of Pathology and Laboratory Medicine,
- ¶Department of Pediatrics, and
- ‡Department of Surgery, University of British Columbia;
- †Immunity in Health & Disease, Child and Family Research Institute, British Columbia Children’s Hospital; and
- §Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada
- Address correspondence and reprint requests to Dr. Rusung Tan, Child and Family Research Institute, British Columbia Children’s Hospital, A4-148, Translational Research Building, 950 West 28th Avenue, Vancouver, British Columbia, V5Z 4H4, Canada. E-mail address: roo{at}interchange.ubc.ca
Abstract
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−CD25intFOXP3low 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−CD25intFOXP3low 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.
Footnotes
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This work was supported in part by grants from the Canadian Institutes of Health Research (IIN-84038 to R.T.; MOP-93793 to M.K.L.) and the Juvenile Diabetes Research Foundation (to R.T.). The authors are all members of the Canadian Institutes of Health Research Systemic Lupus Erythematosus and Diabetes Team for Childhood Autoimmunity. A.K.M. (Child and Family Research Institute) and S.Q.C. (Michael Smith Foundation for Health Research) hold graduate studentship awards. C.P. holds salary awards from the Child and Family Research Institute and the Canadian Diabetes Association. M.K.L. is a Canada Research Chair in Transplantation and R.T. is a senior scholar of the Michael Smith Foundation for Health Research.
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The online version of this article contains supplemental material.
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Abbreviations used in this paper:
- FMO
- fluorescence-minus-one
- Fr.
- fraction
- T1D
- type 1 diabetes
- Treg
- regulatory T cell.
- Received June 7, 2010.
- Accepted August 6, 2010.
- Copyright © 2010 by The American Association of Immunologists, Inc.
