Regulation of thymocyte trafficking by Tagap, a GAP domain protein linked to human autoimmunity

Jonathan S. Duke-Cohan; Yuki Ishikawa; Akihiro Yoshizawa; Young-Il Choi; Chin-Nien Lee; Oreste Acuto; Stephan Kissler; Ellis L. Reinherz

doi:10.1126/scisignal.aan8799

Research ArticleImmunology

Regulation of thymocyte trafficking by Tagap, a GAP domain protein linked to human autoimmunity

Jonathan S. Duke-Cohan¹,²,*,
Yuki Ishikawa²,³,
Akihiro Yoshizawa¹,²,†,
Young-Il Choi¹,²,‡,
Chin-Nien Lee²,³,§,
Oreste Acuto ⁴,
Stephan Kissler²,³,*, and
Ellis L. Reinherz¹,²,*

¹Laboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
²Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
³Immunobiology Section, Joslin Diabetes Center, Boston, MA 02215, USA.
⁴Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.

↵*Corresponding author. Email: ellis_reinherz{at}dfci.harvard.edu (E.L.R.); jonathan_duke-cohan{at}dfci.harvard.edu (J.S.D.-C.); stephan.kissler{at}joslin.harvard.edu (S.K.)

↵† Present address: Laboratory for Innate Immune Systems, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
↵‡ Present address: Pharmacology Lab, Chong Kun Dang Research Institute, 315-20 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si, Gyeonggi-do 446-916, Republic of Korea.
↵§ Present address: Boston Children’s Hospital, Enders Research Building BCH3097, 300 Longwood Avenue, Boston, MA 02115, USA.

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Sci. Signal. 12 Jun 2018:
Vol. 11, Issue 534, eaan8799
DOI: 10.1126/scisignal.aan8799

Jonathan S. Duke-Cohan

Laboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

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ORCID record for Jonathan S. Duke-Cohan
For correspondence: ellis_reinherz@dfci.harvard.edujonathan_duke-cohan@dfci.harvard.edustephan.kissler@joslin.harvard.edu

Yuki Ishikawa

Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.Immunobiology Section, Joslin Diabetes Center, Boston, MA 02215, USA.

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ORCID record for Yuki Ishikawa

Akihiro Yoshizawa

Laboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

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Young-Il Choi

Laboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

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Chin-Nien Lee

Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.Immunobiology Section, Joslin Diabetes Center, Boston, MA 02215, USA.

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Oreste Acuto

Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.

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Stephan Kissler

Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.Immunobiology Section, Joslin Diabetes Center, Boston, MA 02215, USA.

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ORCID record for Stephan Kissler
For correspondence: ellis_reinherz@dfci.harvard.edujonathan_duke-cohan@dfci.harvard.edustephan.kissler@joslin.harvard.edu

Ellis L. Reinherz

Laboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

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ORCID record for Ellis L. Reinherz
For correspondence: ellis_reinherz@dfci.harvard.edujonathan_duke-cohan@dfci.harvard.edustephan.kissler@joslin.harvard.edu

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Letting thymocytes go

During the process of T cell development, thymocytes must travel from the cortex of the thymus to the medulla, where any potentially autoreactive cells are removed by negative selection. This translocation is mediated by interactions between sema3E, which is secreted from the medulla, and its receptor plexin-D1, which is present on thymocytes in the cortex. Duke-Cohan et al. found that mouse thymocytes lacking the GTPase-activating protein Tagap had defective sema3E/plexin-D1 signaling and thus failed to detach from the cortex. Given that single-nucleotide polymorphisms in the gene encoding TAGAP are associated with autoimmune disorders, these data suggest that Tagap facilitates the trafficking required for the efficient negative selection of autoreactive cells.

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Regulation of thymocyte trafficking by Tagap, a GAP domain protein linked to human autoimmunity

Letting thymocytes go

Sci. Signal.

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