Identification of a T follicular helper cell subset that drives anaphylactic IgE

被引：344

作者：

Gowthaman, Uthaman ^{[1
,2
]}

Chen, Jennifer S. ^{[1
,2
]}

Zhang, Biyan ^{[1
,2
]}

Flynn, William F. ^{[3
]}

Lu, Yisi ^{[2
]}

Song, Wenzhi ^{[2
]}

Joseph, Julie ^{[1
]}

Gertie, Jake A. ^{[1
,2
]}

Xu, Lan ^{[1
,2
]}

Collet, Magalie A. ^{[3
]}

Grassmann, Jessica D. S. ^{[3
]}

Simoneau, Tregony ^{[4
]}

Chiang, David ^{[5
,6
]}

Berin, M. Cecilia ^{[5
,6
]}

Craft, Joseph E. ^{[2
]}

Weinstein, Jason S. ^{[7
]}

Williams, Adam ^{[3
,8
]}

Eisenbarth, Stephanie C. ^{[1
,2
]}

机构：

[1] Yale Univ, Sch Med, Dept Lab Med, 333 Cedar St, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06520 USA

[3] Jackson Lab Genom Med, Farmington, CT 06030 USA

[4] CT Childrens Med Ctr, Asthma Ctr, Hartford, CT 06106 USA

[5] Icahn Sch Med Mt Sinai, Jaffe Food Allergy Inst, New York, NY 10029 USA

[6] Icahn Sch Med Mt Sinai, Precis Immunol Inst, New York, NY 10029 USA

[7] Rutgers New Jersey Med Sch, Ctr Immun & Inflammat, Newark, NJ 07101 USA

[8] Univ Connecticut, Ctr Hlth, Dept Genet & Genome Sci, Farmington, CT 06032 USA

来源：

SCIENCE | 2019年 / 365卷 / 6456期

关键词：

BCL6; EXPRESSION; TH2; CELLS; IN-VIVO; IL-4; DIFFERENTIATION; TRANSCRIPTION; AFFINITY; IMMUNITY; RECEPTOR; RESPONSES;

D O I：

10.1126/science.aaw6433

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cross-linking of high-affinity immunoglobulin E (IgE) results in the life-threatening allergic reaction anaphylaxis. Yet the cellular mechanisms that induce B cells to produce IgE in response to allergens remain poorly understood. T follicular helper (T-FH) cells direct the affinity and isotype of antibodies produced by B cells. Although T-FH cell-derived interleukin-4 (IL-4) is necessary for IgE production, it is not sufficient. We report a rare population of IL-13-producing T-FH cells present in mice and humans with IgE to allergens, but not when allergen-specific IgE was absent or only low-affinity. These "T(FH)13" cells have an unusual cytokine profile (IL-13(hi)IL-4(hi)IL-5(hi)IL-21(lo)) and coexpress the transcription factors BCL6 and GATA3. T(FH)13 cells are required for production of high-but not low-affinity IgE and subsequent allergen-induced anaphylaxis. Blocking T(FH)13 cells may represent an alternative therapeutic target to ameliorate anaphylaxis.

引用

页码：883 / +

页数：63

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