Evidence that Cd101 is an autoimmune diabetes gene in nonobese diabetic mice

Daniel B. Rainbow; Carolyn Moule; Heather I. Fraser; Jan Clark; Sarah K. Howlett; Oliver Burren; Mikkel Christensen; Val Moody; Charles A. Steward; Javid P. Mohammed; Michael E. Fusakio; Emma L. Masteller; Erik B. Finger; J. P. Houchins; Dieter Naf; Frank Koentgen; William M. Ridgway; John A. Todd; Jeffrey A. Bluestone; Laurence B. Peterson; Jochen Mattner; Linda S. Wicker

doi:10.4049/jimmunol.1003523

Evidence that Cd101 is an autoimmune diabetes gene in nonobese diabetic mice

Daniel B. Rainbow, Carolyn Moule, Heather I. Fraser, Jan Clark, Sarah K. Howlett, Oliver Burren, Mikkel Christensen, Val Moody, Charles A. Steward, Javid P. Mohammed, Michael E. Fusakio, Emma L. Masteller, Erik B. Finger, J. P. Houchins, Dieter Naf, Frank Koentgen, William M. Ridgway, John A. Todd, Jeffrey A. Bluestone, Laurence B. PetersonJochen Mattner, Linda S. Wicker

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Abstract

We have previously proposed that sequence variation of the CD101 gene between NOD and C57BL/6 mice accounts for the protection from type 1 diabetes (T1D) provided by the insulin-dependent diabetes susceptibility region 10 (Idd10), a <1 Mb region on mouse chromosome 3. In this study, we provide further support for the hypothesis that Cd101 is Idd10 using haplotype and expression analyses of novel Idd10 congenic strains coupled to the development of a CD101 knockout mouse. Susceptibility to T1D was correlated with genotype-dependent CD101 expression on multiple cell subsets, including Foxp3⁺ regulatory CD4⁺ T cells, CD11c⁺ dendritic cells, and Gr1⁺ myeloid cells. The correlation of CD101 expression on immune cells from four independent Idd10 haplotypes with the development of T1D supports the identity of Cd101 as Idd10. Because CD101 has been associated with regulatory T and Ag presentation cell functions, our results provide a further link between immune regulation and susceptibility to T1D.

Original language	English (US)
Pages (from-to)	325-336
Number of pages	12
Journal	Journal of Immunology
Volume	187
Issue number	1
DOIs	https://doi.org/10.4049/jimmunol.1003523
State	Published - Jul 1 2011

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Rainbow, D. B., Moule, C., Fraser, H. I., Clark, J., Howlett, S. K., Burren, O., Christensen, M., Moody, V., Steward, C. A., Mohammed, J. P., Fusakio, M. E., Masteller, E. L., Finger, E. B., Houchins, J. P., Naf, D., Koentgen, F., Ridgway, W. M., Todd, J. A., Bluestone, J. A., ... Wicker, L. S. (2011). Evidence that Cd101 is an autoimmune diabetes gene in nonobese diabetic mice. Journal of Immunology, 187(1), 325-336. https://doi.org/10.4049/jimmunol.1003523

Rainbow, DB, Moule, C, Fraser, HI, Clark, J, Howlett, SK, Burren, O, Christensen, M, Moody, V, Steward, CA, Mohammed, JP, Fusakio, ME, Masteller, EL, Finger, EB, Houchins, JP, Naf, D, Koentgen, F, Ridgway, WM, Todd, JA, Bluestone, JA, Peterson, LB, Mattner, J & Wicker, LS 2011, 'Evidence that Cd101 is an autoimmune diabetes gene in nonobese diabetic mice', Journal of Immunology, vol. 187, no. 1, pp. 325-336. https://doi.org/10.4049/jimmunol.1003523

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abstract = "We have previously proposed that sequence variation of the CD101 gene between NOD and C57BL/6 mice accounts for the protection from type 1 diabetes (T1D) provided by the insulin-dependent diabetes susceptibility region 10 (Idd10), a <1 Mb region on mouse chromosome 3. In this study, we provide further support for the hypothesis that Cd101 is Idd10 using haplotype and expression analyses of novel Idd10 congenic strains coupled to the development of a CD101 knockout mouse. Susceptibility to T1D was correlated with genotype-dependent CD101 expression on multiple cell subsets, including Foxp3+ regulatory CD4+ T cells, CD11c+ dendritic cells, and Gr1+ myeloid cells. The correlation of CD101 expression on immune cells from four independent Idd10 haplotypes with the development of T1D supports the identity of Cd101 as Idd10. Because CD101 has been associated with regulatory T and Ag presentation cell functions, our results provide a further link between immune regulation and susceptibility to T1D.",

author = "Rainbow, {Daniel B.} and Carolyn Moule and Fraser, {Heather I.} and Jan Clark and Howlett, {Sarah K.} and Oliver Burren and Mikkel Christensen and Val Moody and Steward, {Charles A.} and Mohammed, {Javid P.} and Fusakio, {Michael E.} and Masteller, {Emma L.} and Finger, {Erik B.} and Houchins, {J. P.} and Dieter Naf and Frank Koentgen and Ridgway, {William M.} and Todd, {John A.} and Bluestone, {Jeffrey A.} and Peterson, {Laurence B.} and Jochen Mattner and Wicker, {Linda S.}",

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Evidence that Cd101 is an autoimmune diabetes gene in nonobese diabetic mice

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