BCAP links IL-1R to the PI3K-mTOR pathway and regulates pathogenic Th17 cell differentiation

Krystin Deason, Ty Dale Troutman, Aakanksha Jain, Dilip K. Challa, Rajakumar Mandraju, Travis Brewer, E. Sally Ward, Chandrashekhar Pasare

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The toll-like receptor (TLR) and interleukin (IL)-1 family of receptors share several signaling components, including the most upstream adapter, MyD88. We previously reported the discovery of B cell adapter for phosphoinositide 3-kinase (BCAP) as a novel toll-IL-1 receptor homology domain-containing adapter that regulates inflammatory responses downstream of TLR signaling. Here we find that BCAP plays a critical role downstream of both IL-1 and IL-18 receptors to regulate T helper (Th) 17 and Th1 cell differentiation, respectively. Absence of T cell intrinsic BCAP did not alter development of naturally arising Th1 and Th17 lineages but led to defects in differentiation to pathogenic Th17 lineage cells. Consequently, mice that lack BCAP in T cells had reduced susceptibility to experimental autoimmune encephalomyelitis. More importantly, we found that BCAP is critical for IL-1R-induced phosphoinositide 3-kinase-Akt-mechanistic target of rapamycin (mTOR) activation, and minimal inhibition of mTOR completely abrogated IL-1β-induced differentiation of pathogenic Th17 cells, mimicking BCAP deficiency. This study establishes BCAP as a critical link between IL-1R and the metabolic status of activated T cells that ultimately regulates the differentiation of inflammatory Th17 cells.

Original languageEnglish (US)
Pages (from-to)2413-2428
Number of pages16
JournalJournal of Experimental Medicine
Volume215
Issue number9
DOIs
StatePublished - Jan 1 2018

Fingerprint

Th17 Cells
1-Phosphatidylinositol 4-Kinase
Interleukins
Sirolimus
Phosphatidylinositol 3-Kinases
Cell Differentiation
B-Lymphocytes
Interleukin-1 Receptors
T-Lymphocytes
Interleukin-1
Interleukin-18 Receptors
Toll-Like Receptor 1
Th1 Cells
Autoimmune Experimental Encephalomyelitis
Toll-Like Receptors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Deason, K., Troutman, T. D., Jain, A., Challa, D. K., Mandraju, R., Brewer, T., ... Pasare, C. (2018). BCAP links IL-1R to the PI3K-mTOR pathway and regulates pathogenic Th17 cell differentiation. Journal of Experimental Medicine, 215(9), 2413-2428. https://doi.org/10.1084/jem.20171810

BCAP links IL-1R to the PI3K-mTOR pathway and regulates pathogenic Th17 cell differentiation. / Deason, Krystin; Troutman, Ty Dale; Jain, Aakanksha; Challa, Dilip K.; Mandraju, Rajakumar; Brewer, Travis; Ward, E. Sally; Pasare, Chandrashekhar.

In: Journal of Experimental Medicine, Vol. 215, No. 9, 01.01.2018, p. 2413-2428.

Research output: Contribution to journalArticle

Deason, K, Troutman, TD, Jain, A, Challa, DK, Mandraju, R, Brewer, T, Ward, ES & Pasare, C 2018, 'BCAP links IL-1R to the PI3K-mTOR pathway and regulates pathogenic Th17 cell differentiation', Journal of Experimental Medicine, vol. 215, no. 9, pp. 2413-2428. https://doi.org/10.1084/jem.20171810
Deason, Krystin ; Troutman, Ty Dale ; Jain, Aakanksha ; Challa, Dilip K. ; Mandraju, Rajakumar ; Brewer, Travis ; Ward, E. Sally ; Pasare, Chandrashekhar. / BCAP links IL-1R to the PI3K-mTOR pathway and regulates pathogenic Th17 cell differentiation. In: Journal of Experimental Medicine. 2018 ; Vol. 215, No. 9. pp. 2413-2428.
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