Immunology Faculty Member - Talal Chatila, MD, M.Sc.

Talal Chatila, MD, M.Sc.

Professor of Pediatrics

Boston Children's Hospital
Karp Family Building, Room 10-214
1 Blackfan St.
Boston, MA 02115
Tel: 617-919-3529
Fax: 617-730-0528
Email: talal.chatila@childrens.harvard.edu



A major focus of our studies has been the elucidation of genetic pathways regulating tolerance and to identify human diseases resulting from defects along those pathways. We have approached this issue from the perspective of Mendelian traits associated with allergic and immunological dysregulatory disorders. Our earlier studies have led to the identification
of human mutations in the transcription factor Foxp3, later revealed to be critical for regulatory T (Treg) cell differentiation and effector function. Treg cell deficiency disorders are associated with myriad allergic and autoimmune manifestations, pursuant to the prevailing intense immune dysregulation. Our recent studies have mobilized mouse and human genetic and
functional approaches to elucidate the precise molecular mechanisms of the breakdown in Treg cell function in these disorders. We also seek to reprogram regulatory function in impaired Treg cells (e.g. those lacking Foxp3, reference 1 below) in a manner that can then be broadly applied to a variety of Treg deficiency-related disorders. We are also interested in the mechanisms by which Treg cells can differentially regulate distinct checkpoints governing allergy and
autoimmunity, such as those involving Treg cell-derived transforming growth factor beta 1(TGF-β1 ) (reference2). We are also interested in understand the role of Treg cell-mediated immune regulation in common allergic inflammatory diseases including allergic airway inflammation in asthma (reference 3 and 4) and oral tolerance breakdown in food allergy (reference 5 and 6), Having established a critical role for tissue Treg cells in the pathogenesis of the respective disorder, we are particularly interested in the molecular and cellular mechanisms by which Treg cells end up licensing tissue inflammation,. Key concepts include the pathological reprogramming of Treg cells to promote T helper cell type 1, 2 and 17 (Th1, Th2 2 and Th17)-dependent inflammation, the nature of the molecular signals that license Treg cell-dependent
tissue inflammation (e.g. Notch4 expression on lung Treg cells) and the role of environmental factors in the process (e.g. air pollutants, microbiota). These these studies are then leveraged to the design of precision therapies for restoring tissuespecific immune tolerance,such as therapy with immunomodulatory commensal bacteria for food allergy (reference 6).



Last Update: 12/18/2020



Publications

1) Charbonnier LM, Cui Y, Stephen-Victor E, Harb H, Lopez D, Bleesing JJ, Garcia-Lloret MI, Chen K, Ozen A, Carmeliet
P, Li MO, Pellegrini M, Chatila TA. Functional reprogramming of regulatory T cells in the absence of Foxp3. Nat Immunol.
2019 Sep;20(9):1208-1219.
2) Turner JA, Stephen-Victor E, Wang S, Rivas MN, Abdel-Gadir A, Harb H, Cui Y, Fanny M, Charbonnier LM, Fong JJH,
Benamar M, Wang L, Burton OT, Bansal K, Bry L, Zhu C, Li QZ, Clement RL, Oettgen HC, Crestani E, Rachid R, Sage
PT, Chatila TA. Regulatory T Cell-Derived TGF-β1 Controls Multiple Checkpoints Governing Allergy and Autoimmunity.
Immunity. 2020 Dec; 53(6): 1202-1214.
3) Massoud A, Charbonnier L-M, Lopez D, Pellegrini M, Phipatanakul W, Chatila TA. An asthma-associated IL4R
polymorphism exacerbates airway inflammation by promoting conversion of regulatory T cells to TH17-like cells. Nat.
Med. 2016 Sep;22(9):1013-22.
4) . Harb H, Stephen-Victor E, Crestani E, Benamar M, Massoud A, Cui Y, Charbonnier LM, Arbag S, Baris S, Cunnigham
A, Leyva-Castillo JM, Geha RS, Mousavi AJ, Guennewig B, Schmitz-Abe K, Sioutas C, Phipatanakul W, Chatila TA. A
regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma. Nat Immunol. 2020 Nov;21(11):1359-1370.
5) Noval Rivas M, Burton OT, Wise P, Charbonnier L-M, Georgiev P, Oettgen HC, Rachid R, Chatila TA. Regulatory T
Cell reprogramming toward a Th2-cell-like lineage impairs oral tolerance and promotes food allergy. Immunity. 2015 Mar
17;42(3):512-23.
6) Abdel-Gadir A, Stephen-Victor E, Gerber GK, Noval Rivas M, Wang S, Harb H, Wang L, Li N, Crestani E, Spielman S,
Secor W, Biehl H, Dibendetto N, X. D, Umetsu DT, Bry L, Rachid R, Chatila TA. Microbiota Therapy Acts Via a
Regulatory T Cell MyD88/RORgt Pathway to Suppress Food Allergy. Nat. Med. 2019 Jul;25(7):1164-1174.



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